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The generation and functions of human peripheral blood (PB) IgM CD27+ B cells to migrate to B-cell follicles and undergo germinal center (GC) B-cell differentiation, whereas activated IgG + memory B cells preferentially showed a plasma cell (PC) fate. This observation was supported by reverse regulation of B-cell lymphoma 6 and PR domain containing 1 and differential BTB and CNC homology 1, basic leucine zipper transcription factor 2 expression. Moreover, IgM

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The present study evaluated cellular and humoral immune parameters in myeloma patients, focusing on the effect of treatment and the risk of opportunistic infections. Peripheral blood lymphocyte subsets and serum levels of nonmyeloma immunoglobulins (Ig) were analysed in 480 blood samples from 77 myeloma patients. Untreated myeloma patients exhibited significantly reduced CD4+/45RO+, CD19+, CD3+/HLA-DR+, and natural killer (NK) cells, as well as nonmyeloma IgA, IgG and IgM. Conventional-dose chemotherapy resulted in significantly reduced CD4+ and even further decline of CD4+/CD45RO+ and CD19+ cells, most notably in relapsed patients. Additional thalidomide treatment had no significant effects on these parameters. Following high-dose chemotherapy (HD-CTX), prolonged immunosuppression was observed. Although CD8+, NK, CD19+ and CD+/CD45RO+ cells recovered to normal values within 60, 90, 360 and 720 days, respectively, CD4+ counts remained reduced even thereafter. Nine opportunistic infections were observed, including five cytomegalovirus (CMV) diseases, one Pneumocystis carinii pneumonia (PCP) and three varicella zoster virus infections with CMV diseases and PCP occurring exclusively after HD-CTX. Opportunistic infections were correlated with severely reduced CD4+, as well as CD4+/CD45RO+ and CD19+ counts. Thus, myeloma patients display cellular and humoral immunodeficiencies, which increase following conventional as well as HD-CTX, and constitute an important predisposing factor for opportunistic infections.

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The G protein L L3 subunit (GNB3) 825T allele is predictive of enhanced Gi protein activation. Studying the influence of C825T allele status on cellular in vitro immune responses towards recall antigens and interleukin-2 stimulation we observed a 2^4-fold, significantly increased proliferation in homozygous 825T (TT) vs. C825 allele (CC) carriers. Furthermore, lymphocyte chemotaxis and CD4 + T cell counts of individuals with TT+TC genotypes were significantly enhanced compared to the CC genotype. In summary, it appears that C825T allele status is highly predictive of immunocompetence and could be a candidate gene in disorders associated with inadequate immune response. ß