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B cells are Lymphocyte s that play a large role in the Humoral Immune Response as opposed to the Cell-mediated Immune Response that is governed by T Cell s.
B cells are produced in the bone marrow of most mammals and are therefore called B cells. The principal function of B cells is to make Antibodies against soluble Antigen s. B cells are an essential component of the Adaptive Immune System .


DEVELOPMENT OF B CELLS

B cells are produced in the Bone Marrow of most mammals. Rabbit s are an exception; their B cells develop in the Appendix-sacculus Rotundus . 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 light (L) and two heavy (H) chains, and the genes specifying them are found in the 'H' chain Locus and the 'L' chain Locus . In the H chain loci there are three regions, 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 L chain locus except there are only two regions, namely V and J. The list below describes the process of immunoglobulin formation at the different stages of B cell development.

  • Progenitor B Cells - Contains Germline H genes, Germline L genes

  • Early Pro-B cells - undergoes D-J rearrangement on the H chains

  • Late Pro-B cells - undergoes V-DJ rearrangement on the H chains

  • Large Pre-B cells - the H chain is VDJ rearranged, Germline L genes

  • Small Pre-B cells - undergoes V-J rearrangement on the L chains

  • Immature B cells - VJ rearranged on L chains, VDJ rearranged on H chains. There is start of expression of IgM receptors.

  • Mature B cells - There is start of expression of IgD


When the B cell fails in any step of the maturation process, it will die by a mechanism called Apoptosis . If it recognizes Self-antigen during the maturation process, the B cell will become suppressed (known as Anergy ) or undergo apoptosis (a process called Negative Selection ). B cells are continuously produced in the bone marrow, but only a small portion of newly made B cells survive to participate in the long-lived peripheral B cell pool.

B cell membrane receptors on which drugs may be active evolve during the B cell life span {Link without Title} . CD20 is present on preB cells, but disappears in mature B cells. TACI, BCMA and BAFF-R are present on immature B cells and mature B cells. The agonist of these 3 receptors is inhibited by Belimumab


FUNCTIONS

The human body makes millions of different types of B cells each day that circulate in the Blood and Lymph performing the role of immune surveillence. 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. 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 .


B cell types


  • Plasma B Cell s (also known as ''plasma cells'') are large B cells that have been exposed to antigen and are producing and secreting large amounts of Antibodies , which assist in the destruction of Microbe s by binding to them and making them easier targets for Phagocyte s 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 .

  • Memory B Cell s 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 Cell s express IgM in greater quantities than IgG and its receptors show polyspecificity, meaning that they have low affinities for many different antigens, but 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.

  • B-2 Cell s are the conventional B cells most texts refer to.



RECOGNITION OF ANTIGEN BY B CELLS

A critical difference between B cells and T Cells is how each lymphocyte "sees" 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

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 Cell s).
B cells that have not been exposed to antigen, also known as ''Naive B cells'', can be activated in a T-cell dependent or independent manner.


T-cell dependent activation

When a B cell ingests a Pathogen , it attaches parts of the pathogen's proteins to a Class II MHC protein. This complex is moved to the outside of the cell membrane, where it can be recognized by a T Lymphocyte , which is compatible with similar structures on the cell membrane of a B Lymphocyte . If the B cell and T cell structures match, the T lymphocyte activates the B lymphocyte, which produces antibodies against the bits of pathogen, called antigen, it has presented on its surface.

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 Th'' cell, the T cell secretes Cytokine s 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 can no longer make the earlier isotypes, IgM or IgD .


T-cell independent activation

Many antigens are T-independent, meaning 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, through so called Pattern Recognition Receptor s, to respond with IgM synthesis in the absence of T cell help. 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).


THE ANCESTRAL ROOTS OF B CELLS


In an October 2006 issue of Nature Immunology , it was reported that certain B-cells of primitive Vertebrates (like Fish and Amphibian s) are capable of Phagocytosis , a function usually associated with cells of the Innate Immune System . The authors of this article 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 1.

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 WORD B-CELL

The abbreviation "B" in B cell originally came from Bursa Of Fabricius , an organ in birds in which avian B Cells mature. When it was discovered that in most mammals B cells are formed in bone marrow, the word B cell continued to be appropriate. The fact that bone and bursa both start with the letter 'B' is a coincidence.


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