B-cell differentiation

FIGURE 90-2. Pathway of normal B-cell differentiation and relationship to B-cell lymphocytes. (Reproduced from Armitage JO, Longo DL. Malignancies in lymphoid cells. In Kasper DL, Braunwald E, Fauci AS, et al, (eds.) Harrison s Principles of Internal Medicine. 16th ed. New York McGraw-Hill 2005 544.)... 

Bowman EP, Campbell JJ, Soler D, et al. Developmental switches in chemokine response profiles during B cell differentiation and maturation. J Exp Med 2000 191 1303-1318. 

CXCR5, and CCR5 during normal B-cell differentiation. The authors propose that the cytoplasmic location of the receptors interferes with migration, thereby accounting for diminished dissemination characteristic of this histologic type. 

Volume 190. Retinoids (Part B Cell Differentiation and Clinical Applications) Edited by Lester Packer... 

Taniguchi, T. 1995. Cytokine signalling through non-receptor protein tyrosine kinases. Science 268, 251-255. Takatsu, K. 1997. Cytokines involved in B cell differentiation and their sites of action. Proceedings of the Society for Experimental Biology and Medicine 215(2), 121-133. 

Although the mechanism of action of IFN-a against HCL is incompletely understood, it most likely relates to IFN-a-induced B-cell differentiation, inhibition of hairy-cell responsiveness to B-cell growth factors, or activation of antineoplastic immune cell function [83]. 

This is converted to an inactive phosphorylated form by a dsRNA-dependent protein kinase205 (Fig. 31-10). The protein kinase also appears to be an interferon-induced protein206 as is the oligo(2 -5 A)-activated RNAse indicated in Fig. 31-10.207 Interferons have effects other than inducing the antiviral state. Thus, human IFN-(32 is identical to a B-cell differentiation factor.208 Both IFN-a and IFN-(3 have antigrowth activity and are currently in use for treatment of some forms of cancer as well as for viral infections.209... 

As previously indicated, the primary cells involved in the immune response are lymphocytes which have a centrally located round nucleus, lack specific granules, and have a basophilic cytoplasm containing free ribosomes. The (thymus-dependent) T-lyniphocytes are involved in cell mediated reactions and also interact with B-Iymphocytes (see later) to regulate the production of antibody, The B cells differentiate into the antibody-producing plasma cells. There is growing evidence that neither T... 

Li, Y.-S., Hayakawa, K., Hardy, R.R. (1993). The regulated expression of B lineage associated genes during B cell differentiation in bone marrow and fetal liver. J. Exp. Med. 178, 951-960. 

B cells recognize native or denatured forms of proteins or carbohydrates in soluble, particulate, or cell-bound form. Activated B cells differentiate into plasma cells and produce antibodies, soluble proteins known as immunoglobulins (Ig), that circulate freely and react specifically with the invoking antigen. There are several classes (called isotypes) of Ig molecules—IgM, IgG, IgA, IgE, and IgD. IgM is the predominant antibody in the primary immune response (following initial exposure to an antigen). IgG usually appears later, following a primary infection, but is the predominant antibody... 

B Cell Differentiation Immunophenotypic Profiles of Normal B Lymphoblasts... 

Tucker AN, Vore SJ, Luster MI. 1986. Suppression on B cell differentiation by 2,3,7,8-tetrachloro-dibenzo-p-dioxin. Mol Pharmacol 29 372-377. 

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-... 

In addition to the observed defect in central B cell silencing, deletion of peripheral autoreactive and polyreactive B cells is clearly defective. In fact, in most RA patients no significant decline in the fraction of autoreactive or polyreactive B cells has been observed during transitional B cell differentiation. In conclusion, both a defect at central and peripheral B cell tolerance contributes to the increased fraction of autoreactive and polyreactive mature B cells in RA patients. 

Nomura, K., H. Kanegane, H. Karasuyama, S. Tsukada, K. Agematsu, G. Murakami, S. Sakazume, M. Sako, R. Tanaka, Y. Kuniya, T. Komeno, S. Ishihara, K. Hayashi, T. Kishimoto, and T. Miyawaki. 2000. Genetic defect in human X-linked agammaglobulinemia impedes a maturational evolution of pro-B cells into a later stage of pre-B cells in the B-cell differentiation pathway. Blood 96 610-617. 

Anderson KC, Bates MP, Slaughenhoupt BL, Pinkus GS, Schlossman SF, Nadler LM. Expression of human B cell-associated antigens on leukemias and lymphomas a model of human B cell differentiation. Blood 1984 63 1424-1433. 

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