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Publication : Bcl-2 obstructs negative selection of autoreactive, hypermutated antibody V regions during memory B cell development.

First Author  Hande S Year  1998
Journal  Immunity Volume  8
Issue  2 Pages  189-98
PubMed ID  9492000 Mgi Jnum  J:88411
Mgi Id  MGI:3032967 Doi  10.1016/s1074-7613(00)80471-9
Citation  Hande S, et al. (1998) Bcl-2 obstructs negative selection of autoreactive, hypermutated antibody V regions during memory B cell development. Immunity 8(2):189-98
abstractText  We analyzed the participation of a predominant B cell clonotype in the anti-arsonate immune response of mice in which Bcl-2 expression was enforced in B cells. Many of the antibodies expressed by the arsonate-induced memory compartment of these mice were 'dual-reactive,' displaying increased affinity acquired via V region somatic hypermutation for both arsonate and the autoantigen DNA. The hypermutated antibodies expressed by the anti-arsonate memory B cell compartment of normal mice have increased affinity for arsonate but lack measurable affinity for DNA. Thus, interference with apoptotic pathways allows developing memory B cells that have acquired autoreactivity to bypass a peripheral tolerance checkpoint. These data demonstrate that both positive and negative selection, working in concert with V gene somatic hypermutation, result in the 'specificity maturation' of the antibody response.
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