B cells developing

Egawa T, Kawabata K, Kawamoto H, et al. The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor. Immunity 2001 15 323-334. 

Wurbel MA, Malissen M, Guy-Grand D, et al. Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor gammadelta(+) gut intraepithelial lymphocytes. Blood 2001 98 2626-2632. 

Hardy RR, Hayakawa K. B cell development pathways. Annu Rev Immunol 2001 19 595-621. 

Yun TJ, Tallquist MD, Aicher A, Rafferty KL, Marshall AJ, Moon JJ, Ewings ME, Mohaupt M, Herring SW, Clark EA (2001) Osteoprotegerin, a crucial regulator of bone metabolism, also regulates B cell development and function. J Immunol 166 1482-1491... 

Weirda, D., et al. Perinatal immunotoxicity of benzene toward mouse B cell development, J. Amer. Coll. Toxicol., 8 981, 1989. 

So-called, B lymphocytes, which constitute about 20% of the total lymphocyte population in the blood, have only one major function which is to synthesize and secrete immunoglobulin antibodies. Following an antigenic challenge, B cells develop into plasma cells whose role is to produce specific immunoglobulin molecules in what is known as the humoral arm of the immune response. 

Minegishi, Y., Rorer, J., Coustan-Smith, E., et al, An essential role for BLNK in human B cell development. Science 286, 1954-1957 (1999). 

Both the nonspecific and specific components of the immune system can be suppressed by chemicals, including drugs. It involves the suppression of maturation and development of immune cells. Both T and B cells develop in the bone marrow and thymus. This involves a complex series of changes in relation to antigen receptors and recognition. Chemicals can affect these processes, leading to a decrease in the number of mature T and B cells. This will result in inhibition of both the humoral and cellular responses. 

Both the B cells and T cells arise in the fetal liver or bone marrow (Fig. 31-1) from pluripotent stem cells. In birds the B cells develop in a special organ, the bursa of Fabricius. Mammalian B cells complete their differentiation into mature lymphocytes within the bone marrow. However, the T cells must travel to the thymus, where they complete their maturation. The T lymphocytes include the previously mentioned NK cells as well as the somewhat similar cytolytic T cells and immunoregulatory T cells. The latter are further characterized as helper T cells41 or suppressor T cells. The adaptive response requires cooperation of helper T cells in many instances. Tire mature B and T cells leave the bone marrow and thymus, which are known as the primary lymphoid tissues, and enter the blood circulation. Following "homing" signals42 they take up residence in a variety of locations... 

There are three different kinds of lymphocytes that have specific functions T cells, B cells and NK cells. T cells develop in the thymus while B cells develop in the adult bone marrow. The thymus and the bone marrow are the primary lymphoid organs where lymphocytes acquire specific cell surface receptors that give them the ability to recognize antigens. NK cells are cytotoxic lymphocytes that develop in the bone marrow. The phagocytes are made up of either monocytes (macrophages) or polymorphonuclear granulocytes, which include neutrophils, eosinophils and basophils. 

Allen, D., Cumano, A., Dildrop, R., Kocks, C., Rajewsky, K., Rajewsky, N., Roes, J., Sablitzky, F., Siekevitz, M. (1987). Timing, genetic requirements and functional consequences of somatic hypermutation during B-cell development. Immunol. Revs. 96, 5-22. 

Ehlich, A., Schaal, S., Gu, H., Kitamura, D., Muller, W., Rajewsky, K. (1993). Immunoglobulin heavy and light chain genes rearrange independently at early stages of B cell development. Cell 72, 695-704. 

McCormack, W.T., Tjoelker, L.W., Thompson, C.B. (1991). Avian B-cell development generation of an immunoglobulin repertoire by gene conversion. Annu. Rev. Immunol. 9,219-241. 

Melchers, F., Karasuyama, H., Haasner, D., Bauer, S., Kudo, A., Sakaguchi, N., Jameson, B., Rolink, A. (1993). The surrogate light chain in B-cell development. Immunology Today 14,60-68. 

Sonoda, E., Pewzner-Jung, Y., Schwers, S., Taki, S., Jung, S., Eilat, D., Rajewsky, K. (1997). B cell development under the condition of allelic inclusion. Immunity 6, 225-233. 

Lymphocytes are one of the primary cell types involved in the immune response. There are two general types of lymphocytes, B and T. Both are derived from bone marrow lymphoid stem cells, but T cells go through an additional maturation process in the thymus. Although the morphology of T cells and B cells is similar, the functions of these two types are distinct. After antigen exposure, B cells develop into antibody-producing plasma cells, whereas T cells are divided into functional subtypes that possess distinct cell surface antigens. 

B cell neoplasms based on morphology, immunophenotype, and genotype often, but not always, correspond to stages of B cell development. However, some B cell lymphomas either do not clearly correspond to a specific developmental stage (i.e., appear to be of variable origin such as chronic lymphocytic leukemia/small lymphocytic lymphoma) or do not appear to be related to any known stage of normal development (i.e., hairy cell leukemia) (H10). 

Induction of Self-Tolerance During B Cell Development... 

Figure 1. Overview of B cell development. B cells are classified into different stages based on rearrangement status of the Ig HC and LC loci. Four major checkpoints for BCR repertoire selection and silencing of autoreactive B cells are indicated 1= pre-BCR checkpoint 2= immature B cell/receptor editing 3= peripheral transitional B cell 4= (lack of) second activation signal.

The final stage of B cell differentiation where the BCR repertoire is shaped is the germinal centre (GC) reaction. In the T cell dependent GC reaction, the BCR is adapted for its cognate antigen by somatic hypermutation (SMH) and class switch recombination (CSR), both of which are driven by activation induced cytidine deaminase (AID). Since AID induces targeted point mutations in the CDRs of the Ig HCs and Ig LCs, this can dramatically alter the BCR affinity or even its specificity. As AID activity may also result in the formation of an autoreactive BCR, a stringent counterselection of such self-reactive B cells is required. By analysis in human of the BCR repertoire of post-GC IgG+ memory B cells, it was demonstrated that indeed new auto-reactive B cells develop by SHM whereas 20% of naive B cells is self-reactive, up to 40% of the IgG+ memory B cells expressed a true de novo created self-reactive BCR. Apparently, lack of T cell help prevents activation of these self-... 

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