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B lymphocytes and plasma cells

B lymphocytes and plasma cells

B lymphocytes are principal cells that mediate humoral adaptive immunity. After their maturation in the bone marrow, B cells enter peripheral lymphoid tissues, which are the sites of interaction with foreign antigens. Production of antibodies is initiated by the interaction of antigens with a small number of mature B cells specific for each antigen. An antigen binds to the membrane receptors on specific B cells and initiates a series of responses that lead to two principal changes: cell proliferation resulting in expansion of the clone, and differentiation to either plasma cells actively secreting antibodies or to memory cells.

Key words: B cells, subsets of B cells, memory B cells, plasma cells


B lymphocytes are principal cells that mediate humoral adaptive immunity. They develop in the bone marrow prior to antigenic stimulation. During their maturation process, they are made to express membrane-bound immunoglobulins that act as antigenic receptors. Every B cells develops a unique B cell-receptor (BCR) that specifically binds and recognises a particular antigenic determinant. After their maturation in the bone marrow, B cells enter peripheral lymphoid tissues, which are the sites of interaction with foreign antigens. Production of antibodies is initiated by the interaction of antigens with a small number of mature B cells specific for each antigen. An antigen binds to the membrane receptors on specific B cells and initiates a series of responses that lead to two principal changes: cell proliferation resulting in expansion of the clone, and differentiation to either plasma cells actively secreting antibodies or to memory cells. At different points in the differentiation of B lymphocytes, different heavy chain isotypes are expressed: immature B cells express IgM, previously unstimulated mature B cells express IgM and IgD, and previously stimulated memory B cells express any Ig isotype. The expression of surface Ig requires its association with other two proteins, called Ig alpha and Ig beta, which function in the transduction of signals generated by antigen binding to membrane immunoglobulin. The complex of the immunoglobulin and transduction molecules is known as B cell receptor (BCR). Its functions is however, substantially enhanced by a B cell co-receptor, which is composed of three molecules: CD21, CD19, and TAPA-1. CD21 recognises fragments of the complement system previously bound to the antigen, C19 transduces the signal and TAPA-1 stabilises both molecules.
In addition to the antigenic receptors, B-cells also express a variety of cell surface proteins that mediate specific B cell functions and biological activities other than antibody production. For instance, CD40 plays a paramount role in B cells cooperation with T cells.
B lymphocytes are not uniform population of cells; they can be subdivided to three subsets: follicular B lymphocytes, B1 B lymphocytes cells, and B2 B lymphocytes.
Most mature naïve B lymphocytes are follicular B cells that constantly recirculate in the blood and migrate from one secondary lymphoid organ to the next in search of antigens. Follicular B cells enter secondary lymphoid tissues (the spleen, lymph nodes, and mucosal lymphoid tissues) through blood vessels and migrate into the primary follicles. The antigens recognised by follicular B cells are of protein nature. They enter the lymphoid organ by afferent lymphatic vessels when they cross an epithelial barrier or by the blood stream. The antigen that is presented to B cells is generally in its intact, native conformation without being processed by antigen-presenting cells (macrophages and dendritic cells); this is the difference between the forms of antigens recognition by B and T lymphocytes.
The activation of antigen-specific B lymphocytes is initiated by the binding of antigen to BCR. B cell activation is facilitated by the co-receptor, which recognises complement fragments covalently attached to the antigen. However, for the full activation, they needs help from a subset of T cells, named T helper cells. Their interaction proceeds on the interface between T cell dependent area (TDA) and B cell dependent area (follicles). Activated B cells migrate towards TDA to meet T lymphocytes that were previously also activated by the same antigens. Mutual interactions between both types of cells make B cells to be fully activated. One fraction of activated B cells will differentiate to short living plasma cells producing antibodies of IgM class and the other fraction returns back to the primary follicle converting it into a secondary follicle. Activated B cells proliferate here extensively and differentiate into either memory B cells or long-living plasma cells. The follicle is now called a germinal centre.
B1 and B2 B cells, contrary to follicular B cells, respond to antigens without any help from the part of T cells. The most important T cell independent (TI) antigens are polysaccharides, glycolipids, and nucleic acids. Most TI antigens are multivalent, being composed of repeated identical antigenic epitopes. Such multivalent antigens induce maximal cross-linking of the BCR complex on specific B cells, leading to their activation and differentiation to plasma cells producing antibodies of IgM class. However, some T cell independent non-protein antigens do induce Ig isotypes other than IgM. For instance, in humans, the dominant antibody class induced by pneumococcal capsular polysaccharide is IgG2.
B1 B cells recognise some autoantigens. Antibodies produced by plasma cells, which differentiate from B1 B cells help to remove old or damaged self-cells or molecules preventing them to induce a potential autoimmune response. They are therefore named as „natural antibodies “. B1 B cells are preponderant especially in foetal life. In the blood stream of the foetus, they are in a high percentage – e.g. in the umbilical cord, they represent 60 till 80%. Their counts slowly decline after delivery, in the blood of adults only 5 % out of all circulating B cells belongs to B1 B cells. They are settled especially in the omentum, in clusters of a lymphoid tissue called „milky patches“; they can be found also in lymph nodes, in their germinal centres. Similarly to follicular B cells, they can differentiate to memory cells.
B2 B cells are settled in the marginal zone of the white pulp of the spleen, in a close vicinity to sinuses; this location caused that they were renamed as marginal zone B cells, the term mostly used nowadays. Their presence in the marginal zones endows them to react promptly to blood born antigens; plasma cells differentiated from produce antibodies of IgM class. After their biological role is over, they die by apoptosis. No memory B cells appear during their proliferation and differentiation.
Memory B cells are generated the germinal centres and are capable of making rapid responses to subsequent introduction of antigen. They survive in the bone marrow for long periods, without continuing antigenic stimulation. Some memory B cells may remain in the lymphoid organ where they were generated, whereas others exit germinal centres and recirculate between the blood and lymphoid organs. Memory B cells typically express high-affinity antigen receptors of IgG, IgA or IgE class. The production of large quantities of high-affinity antibodies is greatly accelerated after secondary exposure to antigens (secondary immune response).
Plasma cells differentiate from activated B cells and produce antibodies in a great quantity: one plasma cell produces app. 1,000 molecules per 1 minute!!! They are characterised especially by abundant endoplasmic reticulum and very conspicuous Golgi apparatus. The endoplasmic reticulum is responsible for synthesis of antibodies and the Golgi apparatus for a post-translation modification of antibodies, i.e. oligosaccharides are added and complete molecules are prepared for their transport to the cell surface.
There are two types of plasma cells, short-living and long-living. The former are generated during T-independent responses and early during T cell–dependent responses in extra-follicular B cell foci. These cells are generally found in secondary lymphoid organs and also in peripheral non-lymphoid tissues. Other plasma cells, plasmablasts, are generated in T-dependent germinal centre responses. They enter the circulation and home to the bone marrow where they differentiate into long-living plasma cells. Plasma cells in the bone marrow continue to secrete antibodies for months or even years after the antigen is no longer present. These antibodies can provide immediate protection if the antigen is encountered later. It is estimated that almost half the antibody pool in the blood of a healthy adult is produced by long-living plasma cells and is specific for antigens that were encountered in the past.

References
Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. 7. Philadelphia: Saunders, Elsevier, 2012: 1545.
Hamel KM, Liarski VM, Clark MR. Germinal center B-cells. Autoimmunity. 2012; 45(5): 333-47.
Murphy K, Janeway ChA, Jr, Travers P, Walport M. Janeway's Immunobiology. 8. New York, London: Garland Science, 2012: 1-868.
Seifert M1, Küppers R. Human memory B cells. Leukemia. 2016; 30(12): 2283-92.
Vinuesa CG, Linterman MA, Goodnow ChC, Randall KL. T cells and follicular dendritic cells in germinal B cell formation and selection. Immunol Rev 2010; 237: 72-89.
Weisel F, Shlomchik M. Memory B Cells of Mice and Humans. Annu Rev Immunol. 2017; in press.
Yuseff MI, Pierobon P, Reversat A, Lennon-Dumenil AM. How B cells capture, process and present antigens: a crucial role for cell polarity. Nat Rev Immunol. 2013; 13(7): 475-8
 

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Keywords: B cells, B cell subsets, memory B cells, plasma cells

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author: Milan Buc | organization: Institute of Immunology | published on: 6.3.2017 | last modified on: 6.3.2017
citation: Buc Milan: B lymphocytes and plasma cells. Multimedia support in the education of clinical and health care disciplines :: Portal of Faculty of Medicine, Comenius University [online] 2017-03-06, last modif. 2017-03-06 [cit. 2018-01-21] Available from WWW: <https://portal.fmed.uniba.sk/articles.php?aid=290>. ISSN 1337-9577.
 

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