B cell
The cells of the immune system that make antibodies to invading pathogens like viruses. They form memory cells that remember the same pathogen for faster antibody production in future infections.
Latin	lymphocytus B
Code	TH H2.00.04.1.02005 TH H2.00.04.3.07002

B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by T cells). B cells are an essential component of the adaptive immune system. B cells, which are the precursors of plasma cells, are characterized by the presence of a B-cell receptor able to bind specifically an antigen. Their principal functions are to make antibodies against antigens, perform the role of antigen-presenting cells (APCs) and eventually develop into memory B cells after activation by antigen interaction. Recently, a new, suppressive function of B cells has been discovered.

The abbreviation "B", in B cell, comes from the bursa of Fabricius in birds, where they mature. In mammals, immature B cells are formed in the bone marrow, which is used as a backronym for the cells' name.^[1]

Development of B cells[link]

Immature B cells are produced in the bone marrow of most mammals. Rabbits are an exception; their B cells develop in the appendix-sacculus rotundus. After reaching the IgM+ immature stage in the bone marrow, these immature B cells migrate to secondary lymphoid tissues (such as the spleen, lymph nodes, Peyer's patches, etc.) where they are called transitional B cells, and some of these cells differentiate into mature B lymphocytes.^[2]

B cell development occurs through several stages, each stage representing a change in the genome content at the antibody loci. An antibody is composed of two identical light (L) and two identical heavy (H) chains, and the genes specifying them are found in the 'V' (Variable) region and the 'C' (Constant) region. In the heavy-chain 'V' region there are three segments; V, D and J, which recombine randomly, in a process called VDJ recombination, to produce a unique variable domain in the immunoglobulin of each individual B cell. Similar rearrangements occur for light-chain 'V' region except there are only two segments involved; V and J. The list below describes the process of immunoglobulin formation at the different stages of B cell development.

When the B cell fails in any step of the maturation process, it will die by a mechanism called apoptosis, here called clonal deletion.^[5] B cells are continuously produced in the bone marrow. When the B cell receptor, on the surface of the cell matches the detected antigens present in the body, the B cell proliferates and secretes a free form of those receptors (antibodies) with identical binding sites as the ones on the original cell surface. After activation, the cell proliferates and B memory cells would form to recognise the same antigen. This information would then be used as a part of the adaptive immune system for a more efficient and more powerful immune response for future encounters with that antigen.

B cell membrane receptors evolve and change throughout the B cell life span.^[6] TACI, BCMA and BAFF-R are present on both immature B cells and mature B cells. All of these 3 receptors may be inhibited by Belimumab. CD20 is expressed on all stages of B cell development except the first and last; it is present from pre-B cells through memory cells, but not on either pre-pro-B cells or plasma cells.^[7]

Immune Tolerance[link]

Like their fellow lymphocytes, the T cells, immature B cells are tested for auto-reactivity by the immune system before leaving the bone marrow. In the bone marrow (the central lymphoid organ), central tolerance is produced. The immature B cells whose B-cell receptors (BCRs) bind too strongly to self antigens will not be allowed to mature. If B cells are found to be highly reactive to self, three mechanisms can occur.

• Clonal deletion: the removal, usually by apoptosis, of B cells of a particular self antigen specificity.
• Receptor editing: the BCRs of self reactive B cells are given an opportunity to rearrange their conformation. This process occurs via the continued expression of the Recombination activating gene (RAG). Through the help of RAG, receptor editing involves light chain gene rearrangement of the B cell receptor. If receptor editing fails to produce a BCR that is less autoreactive, apoptosis will occur. Note that defects in the RAG-1 and RAG-2 genes are implicated in Severe Combined Immunodeficiency (SCID). The inability to recombine and generate new receptors lead to failure of maturity for both B cells and T cells.

• Anergy: B cells enter a state of permanent unresponsiveness when they bind with weakly cross-linking self antigens that are small and soluble.

Functions[link]

The human body makes millions of different types of B cells each day that circulate in the blood and lymphatic system performing the role of immune surveillance. They do not produce antibodies until they become fully activated. Each B cell has a unique receptor protein (referred to as the B cell receptor (BCR)) on its surface that will bind to one particular antigen. The BCR is a membrane-bound immunoglobulin, and it is this molecule that allows the distinction of B cells from other types of lymphocyte, as well as being the main protein involved in B cell activation. Once a B cell encounters its cognate antigen and receives an additional signal from a T helper cell, it can further differentiate into one of the two types of B cells listed below (plasma B cells and memory B cells). The B cell may either become one of these cell types directly or it may undergo an intermediate differentiation step, the germinal center reaction, where the B cell will hypermutate the variable region of its immunoglobulin gene ("somatic hypermutation") and possibly undergo class switching. Other functions for B cells include antigen presentation, cytokine production and lymphoid tissue organization.

Clonality[link]

B cells exist as clones. All B cells derive from a particular cell, and thus, the antibodies their differentiated progenies (see below) produce can recognize and/or bind the same specific surface components composed of biological macromolecules (epitope) of a given antigen. Such clonality has important consequences, as immunogenic memory relies on it. The great diversity in immune response comes about because there are up to 10⁹ clones with specificities for recognizing different antigens. A single B cell or a clone of cells with shared specificity, upon encountering its specific antigen, divides to produce many B cells. Most of such B cells differentiate into plasma cells that secrete antibodies into blood that bind the same epitope that elicited proliferation in the first place. A small minority survives as memory cells that can recognize only the same epitope. However, with each cycle, the number of surviving memory cells increases. The increase is accompanied by affinity maturation which induces the survival of B cells that bind to the particular antigen with high affinity. This subsequent amplification with improved specificity of immune response is known as secondary immune response. B cells that encounter antigen for the first time are known as naive B cells.

B cell types[link]

A suspected plasma cell. Plasma cells are normally detected in tissue rather than circulation.

• Plasma B cells (also known as plasma cells, plasmocytes, and effector B cells) are large B cells that have been exposed to antigen and produce and secrete large amounts of antibodies, which assist in the destruction of microbes by binding to them and making them easier targets for phagocytes and activation of the complement system. They are sometimes referred to as antibody factories. An electron micrograph of these cells reveals large amounts of rough endoplasmic reticulum, responsible for synthesizing the antibody, in the cell's cytoplasm. These are short lived cells and undergo apoptosis when the inciting agent that induced immune response is eliminated. This occurs because of cessation of continuous exposure to various colony stimulating factors required for survival.

• Memory B cells are formed from activated B cells that are specific to the antigen encountered during the primary immune response. These cells are able to live for a long time, and can respond quickly following a second exposure to the same antigen.

• B-1 cells express IgM in greater quantities than IgG and their receptors show polyspecificity, meaning that they have low affinities for many different antigens. Polyspecific immunoglobulins often have a preference for other immunoglobulins, self antigens and common bacterial polysaccharides. B-1 cells are present in low numbers in the lymph nodes and spleen and are instead found predominantly in the peritoneal and pleural cavities.^[8][9]

• B-2 cells are the conventional B cells most texts refer to.^{[citation needed]}
• Marginal-zone B cells
• Follicular B Cells

Recognition of antigen by B cells[link]

Mechanism of action.

T cell-dependent B cell activation, showing a TH2-cell (left), B cell (right), and several interaction molecules

A critical difference between B cells and T cells is how each lymphocyte recognizes its antigen. B cells recognize their cognate antigen in its native form. They recognize free (soluble) antigen in the blood or lymph using their BCR or membrane bound-immunoglobulin. In contrast, T cells recognize their cognate antigen in a processed form, as a peptide fragment presented by an antigen presenting cell's MHC molecule to the T cell receptor.

Activation of B cells[link]

B cell recognition of antigen is not the only element necessary for B cell activation (a combination of clonal proliferation and terminal differentiation into plasma cells). B cells that have not been exposed to antigen, also known as naïve B cells, can be activated in a T cell-dependent or -independent manner.

T cell-dependent activation[link]

Once a pathogen is ingested by an antigen-presenting cell such as a macrophage or dendritic cell, the pathogen's proteins are then digested to peptides and attached to a class II MHC protein. This complex is then moved to the outside of the cell membrane. The macrophage is now activated to deliver multiple signals to a specific T cell that recognizes the peptide presented. The T cell is then stimulated to produce autocrines (Refer to Autocrine signalling), resulting in the proliferation and differentiation to effector and memory T cells. Helper T cells (i.e. CD4+ T cells) then activate specific B cells through a phenomenon known as an Immunological synapse. Activated B cells subsequently produce antibodies which assist in inhibiting pathogens until phagocytes (i.e. macrophages, neutrophils) or the complement system for example clears the host of the pathogen(s).

Most antigens are T-dependent, meaning T cell help is required for maximal antibody production. With a T-dependent antigen, the first signal comes from antigen cross linking the B cell receptor (BCR) and the second signal comes from co-stimulation provided by a T cell. T dependent antigens contain proteins that are presented on B cell Class II MHC to a special subtype of T cell called a Th2 cell. When a B cell processes and presents the same antigen to the primed T_h cell, the T cell secretes cytokines that activate the B cell. These cytokines trigger B cell proliferation and differentiation into plasma cells. Isotype switching to IgG, IgA, and IgE and memory cell generation occur in response to T-dependent antigens. This isotype switching is known as Class Switch Recombination (CSR). Once this switch has occurred, that particular B cell will usually no longer make the earlier isotypes, IgM or IgD.

T cell-independent activation[link]

Many antigens are T cell-independent in that they can deliver both of the signals to the B cell. Mice without a thymus (nude or athymic mice that do not produce any T cells) can respond to T independent antigens. Many bacteria have repeating carbohydrate epitopes that stimulate B cells, by cross-linking the IgM antigen receptors in the B cell, responding with IgM synthesis in the absence of T cell help. Conjugate vaccines are made to provide a stronger immune response against these foreign molecules. There are two types of T cell independent activation; Type 1 T cell-independent (polyclonal) activation, and type 2 T cell-independent activation (in which macrophages present several of the same antigen in a way that causes cross-linking of antibodies on the surface of B cells).

T cell independent activation type 1 is when a B cell binds to an antigen and receives secondary activation by toll-like receptors; type 2 is when the antigen is a molecule with multiple repeating subunits which can simultaneously cross link enough B cell receptors to fully activate the B cell.

In 2011, it was discovered that immortalized rhesus monkey B cells may be activated by the binding of monoamine ligands to TAAR1, a recently discovered GPCR. They found that methamphetamine, a potent TAAR1 agonist, signals PKA and PKC activation following ligand binding to TAAR1.^[10] Although it is largely recognized as an important regulator of monoaminergic systems, TAAR1 has only recently been characterized as being important for T cell-independent lymphocyte activation.

The ancestral roots of B cells[link]

In an October 2006 issue of Nature Immunology, certain B cells of basal vertebrates (like fish and amphibians) were shown to be capable of phagocytosis, a function usually associated with cells of the innate immune system. The authors postulate that these phagocytic B cells represent the ancestral history shared between macrophages and lymphocytes. B cells may have evolved from macrophage-like cells during the formation of the adaptive immune system.^[11]

B cells in humans (and other vertebrates) are nevertheless able to endocytose antibody-fixed pathogens, and it is through this route that MHC Class II presentation by B cells is possible, allowing Th2 help and stimulation of B cell proliferation. This is purely for the benefit of MHC Class II presentation, not as a significant method of reducing the pathogen load.

Origin of the term[link]

The abbreviation "B" in B cell originally came from Bursa of Fabricius, an organ in birds in which avian B cells mature.^[12] When it was discovered that in most mammals immature B cells are formed in bone marrow, the word B cell continued to be used, although other blood cells also originate from pluripotent stem cells in the bone marrow. The fact that bone and bursa both start with the letter 'B' is a coincidence.

B cell-related pathology[link]

Aberrant antibody production by B cells is implicated in many autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. B cells are also susceptible to malignant transformation.

Additional image[link]

Figure 1: Schematic diagram to explain mechanisms of clonal selection of B cell, and how secondary immune response is stronger, quicker and more specific in comparison with the primary one.^[13]

See also[link]

• Affinity maturation
• Antibody
• Clonal selection
• Original antigenic sin

References[link]

Activation of B Lymphocytes by T-Independent Antigens. Gary Kaiser. American Society for Microbiology. July 2005.

External links[link]

• B-Lymphocytes at the US National Library of Medicine Medical Subject Headings (MeSH)
• B Cells and T Cells
• B Cell Development and Generation of Lymphocyte Diversity
• Interactive Animation of B Cell Maturation (requires Flash video software)
• A Tale of Two SHEPherds (from Beaker Blog)
• Educational Resource on the Biology of Antibody Cells

Personal details
Born	Middlesbrough, England, UK

Paul Vallely CMG is a leading British writer on Africa and development issues. He first coined, in his seminal 1990 book Bad Samaritans: First World Ethics and Third World Debt, the expression that campaigners needed to move "from charity to justice" – a slogan that was taken up by Jubilee 2000 and Live 8.

Vallely was correspondent for The Times in Ethiopia during the great famine of 1984/5. He was commended as International Reporter of the Year for his reports which Bob Geldof described as "vivid, intelligent, moving and brave".^[1] Vallely was the only British correspondent to leave the easy air routes to the feeding camps and strike off across country to find out what was really going on.^[2] He uncovered a number of scandals the Marxist government were trying to keep hidden, was pronounced “an enemy of the revolution”, arrested by the secret police and was expelled from the country. He subsequently reported from across Africa, and elsewhere, covering wars and events in 30 different countries across the globe.

In 2004/5 he was co-author of the report of the Commission for Africa set up by the British prime minister, Tony Blair, of which Bob Geldof was a member. Vallely ghost-wrote Geldof's autobiography, Is That It? in 1985 and travelled with Bob Geldof across Africa to decide how to spend the £100m raised by Live Aid and was involved in the organisation of Live 8.

Bob Geldof paid tribute to his influence in a lecture to the Bar Human Rights Committee Lecture, St. Paul’s Cathedral in which he said: "In his book Bad Samaritans of 1990 Paul Vallely wrote correctly: 'For all his skill as a populist Bob Geldof could not shift the agenda from one of charity to one of justice.” Well maybe after 20 years we’ve finally got there." The founders of Jubilee 2000, Martin Dent and Bill Peters, have also acknowledged being inspired by Vallely's book. (The book is sometimes confused with the 2007 text Bad Samaritans: Rich Nations, Poor Policies and the Threat to the Developing World by the economist Ha-Joon Chang which also argues that the current economic policies supported by the IMF and wealthy countries are hindering development and creating poverty.)

Vallely has chaired or been active in a number of prominent UK aid agencies, including Traidcraft, the Catholic Institute for International Relations (CIIR), Christian Aid and CAFOD. He has been an adviser to the Catholic Bishops of England and Wales and was the author of their report A place of redemption: a Christian approach to punishment and prison.^[3] (Catholic Bishop's Conference of England & Wales, 2004).

He is the associate editor of the UK newspaper The Independent where he writes about ethical, cultural and political issues. (He was once referred to by Peter Wilby in New Statesman as "the Independent's resident saint"^[4]). He is also a columnist for The Church Times and Third Way Magazine. He is a director of The Tablet.

Vallely was created a Companion of St Michael and St George (CMG) "for services to journalism and to the developing world" on 17 June 2006.

He is an Honorary Research Fellow in the School of Arts, Histories and Cultures at the University of Manchester.

In 2008 he was shortlisted for the Orwell Prize, the pre-eminent prize in Britain for political writing.

References[link]

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Publications[link]

• With Geldof in Africa (with David Blundy), 1985;
• Is That It? (with Bob Geldof), 1986;
• Bad Samaritans: First World Ethics and Third World Debt, 1990;
• Promised Lands: Stories of Power and Poverty in the Third World, 1992;
• Daniel and the Mischief Boy (for children), 1993;
• The New Politics: Catholic Social Teaching for the 21st century, 1999;
• The Church and the New Age, 2000;
• Live Aid DVD sleeve notes 2004;
• A Place of Redemption: A Christian approach to Punishment and Prison (ed), 2004;
• The Fifth Crusade: George Bush and the Christianisation of the war in Iraq, 2004;
• Our Common Interest: report of the Prime Minister’s Commission for Africa (co-author) 2005;
• Live 8 Official Programme notes 2005;
• Live 8 DVD sleeve notes 2005;
• Geldof in Africa (with Bob Geldof), 2005;
• Hello World: the official Live 8 Book, 2005;
• "New Labour and the New World Order" in Remoralising Britain, 2008 .
• How Islamic inventors changed the world 2006

External links[link]

• http://www.paulvallely.com
• http://www.commissionforafrica.org/english/about/secretariat-vallely.html Paul Vallely
• http://journalisted.com/paul-vallely
• http://www.highbeam.com/paul.vallely
• http://www.independent.co.uk/paul.vallely
• http://www.churchtimes.co.uk/paul.vallely

The Young Gunz is an American rap duo from Philadelphia, Pennsylvania composed of Young Chris (born Chris Ries in 1983) and Neef Buck (born Hanif Muhammad in 1985). The group is part of Beanie Sigel's State Property collective and was signed to Roc-A-Fella Records. Young Gunz' debut single, "Can't Stop, Won't Stop", made the top 20 on the Billboard charts in 2003.They are currently signed to G-Unit Philly as State Property and Young Gunz but only Young Chris is also signed as a solo-artist.

History[link]

State Property[link]

Ries and Muhammad had been friends since they were young boys on the block(C-Ave).^[1] On "Takeover", a track from his 2001 album The Blueprint, Jay-Z announced the duo as "Chris & Neef".^[2]

In 2001, the duo performed on the State Property soundtrack album.^[2] Chris and Neef starred in the titular movie. Also during this period of their career, Young Chris appeared throughout Dame Dash's Dream Team compilation, and Beanie Sigel's The Reason. The duo performed together on guest appearances for albums like Jay-Z's The Blueprint 2, Freeway's Philadelphia Freeway, State Property's The Chain Gang Vol. 2, and Memphis Bleek's M.A.D.E.; all while recording their album.

The Young Gunz scored their first hit with "Can't Stop, Won't Stop", the lead-off single from the Chain Gang, Vol. 2 album. Its song and video received major airplay on hip-hop radio, MTV2, and BET^[3] and reached #14 on the U.S. Billboard 200 chart and #6 on the Billboard Hot Rap Tracks chart.

As a group[link]

After the success of their single, "Can't Stop, Won't Stop", the label jumped and was ready to release their debut album, Tough Luv. It included the remix to "Can't Stop, Won't Stop", which featured St. Louis rapper Chingy. Singles included "No Better Love" featuring former Roc-A-Fella Records crooner Rell and the Just Blaze-produced "Friday Night". Tough Luv debuted on the Billboard 200 at #3 after selling 128,000 copies in its first week. That week, the album at #2 was labelmate Kanye West's debut album The College Dropout, which was released just two weeks earlier.^[4]

After a brief hiatus, the duo returned with Swizz Beatz produced "Set It Off" from their second album, Brothers from Another. This albums, which was released May, 24th 2005, sales were somewhat of a disappointment compared to the first, despite the decent exposure of the lead single, promotion from Jay-Z himself, TV, radio & magazine appearances. It was the second release from the "new" Roc-A-Fella Records, referencing when Jay-Z became president of Def Jam Records, the first being Memphis Bleek's 534. The album debuted on the Billboard 200 at #15, and included guest features from Kanye West, Swizz Beatz, Slim of 112 (Marvin Scandrick III) and John Legend.^[5]

Disputes with other rap artists[link]

The Young Gunz were part of a public beef and a war of words with West Coast rapper, The Game. The feud stems from The Game's beef with Memphis Bleek, which escalated into a beef with the entire Roc-A-Fella camp with the exception of Kanye West, Jay-Z and Just Blaze. The Game dissed Bleek and The Young Gunz on his 15-minute freestyle track "300 Bars and Runnin'".^[6] The Young Gunz, along with Pooda Brown, responded with a freestyle of their own. Surprisingly, Chris & Neef also beefed with actor, comedian and now rapper, Katt "Money Mike" Wiliams. This beef stemmed from "Set It Off" by the Young Gunz, in which they called a character from a movie that Katt Williams played as, a "fake ass pimp." This beef was encouraged by The Game as he and Katt dissed the two on a Freestyle over their own "Set It Off" beat.^[7]

Young Chris solo work[link]

As early as March 2006, Young Chris thought about recording a solo album. He initially titled it Now or Never.^[8] He stated to XXL magazine that he wanted to release a solo album by the end of 2008 and had been "95 percent done" by June 2008. In this article, Chris also states that he feels himself up there with Lil' Wayne and Juelz Santana.^[9] Since this time, Chris has taken to the internet to solidify himself as a top solo artist, with his YoungChris.com Social Network, hitting the remix circuit, and his much anticipated "The Network" Mixtape series, hosted by DJ Don Cannon. Later in 2010 signed with Division 1, a label started by Rico Love, under the Universal/Motown umbrella. Rico considers Young Chris his flagship artist, working closely with Chris on his debut album and pre-album/mixtape. The mixtape, called "The Re-Introduction", was released on November 20, 2010. The aptly titled mixtape gives the spotlight to a newly signed Young Chris, as a solo artist, and also, re-introduces the combination of DJ Drama and Don Cannon, the former "Affiliates" partners, hosting their first mixtape together, in several years.^[10]

On January 28, a song called "Philly Shit (Mega Mix)" featuring Eve, Black Thought, Money Malc, Fat Joe, Fred The Godson, Diggy Simmons, Jermaine Dupri & Game was leaked.^[11]

Discography[link]

Solo albums[link]

• Tough Luv (2004)
• Brothers from Another (2005)

Collaboration albums[link]

• State Property (with State Property) (2002)
• The Chain Gang Vol. 2 (with State Property) (2003)
• The Chain Gang Vol. 3 (with State Property) (TBA)

Filmography[link]

• State Property 2 (2005)
• Fade to Black (2004)
• State Property (2002)

References[link]

External links[link]

• Chris & Neef Website
• MTV.com Young Gunz profile

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Les Twins
Background information
Born	(1988-12-06) December 6, 1988 (age 23)
Origin	Sarcelles, Val d'Oise, France
Genres	New Style, Hip-hop dance
Associated acts	Cirque Du Soleil, Criminalz Crew, Veteranz Crew
Website	https://www.facebook.com/pages/Les-TWINS-Organization-Official/109855652372782?sk=info
Members
Laurent Nicolas Bourgeois Larry Nicolas Bourgeois

Larry and Laurent Bourgeois, popularly known as "Les Twins" or Larry " Ca Blaze " Bourgeois and Laurent " Lil Beast " Bourgeois, are a hip hop dance duo originating from Sarcelles, France. The twin brothers who are of Guadeloupean descent (Guadeloupe, F.W.I.), are known worldwide for their talents in New Style dancing. Although they can be seen dancing as a duet, they are also a part of a larger crew known as Criminalz Crew, a group with a variety of dancers that range from b-boys to other new style dancers such as themselves. Les Twins have appeared on the television show Incroyable Talent^[1] as well as the Ellen DeGeneres Show. Les Twins have competed in multiple dance competitions such as: World Of Dance, Battle Of The Stylez, Urban Dance Showcase and won the Juste Debout Dance Competition in the Hip-Hop New Style category in 2011. ^{[2][original research?]} They come from a very large family with 18 siblings, and only 9 of whom dance.

Les Twins have performed with Beyoncé Knowles^[3].^[4] They have also appeared in Jay-Z's That's Rocawear viral video^[5] and the music video for "La Gloria" by French-Argentine band Gotan Project. They were also traveling with Cirque du Soleil Michael Jackson Immortal World Tour as dancers with a newly formed crew especially for the tour, named Veteranz crew until sometime in 2012.

Les Twins are represented by Next Model Management.

Gallery[link]

• 

  Les Twins photo shoot with Shawn Welling

• 

  Les Twins in action

• 

  Les Twins mid-air during a shoot with Shawn Welling

References[link]

External links[link]

• Les Twins Official Contacts: https://www.facebook.com/pages/Les-TWINS-Organization-Official/109855652372782?sk=info