Enforced Expression of Bcl-2 Selectively Perturbs Negative Selection of Dual Reactive AntibodiesReport as inadecuate

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Developmental Immunology - Volume 8 2001, Issue 3-4, Pages 223-234

Department of Microbiology and Immunology, The Kimmel Cancer Institute, Thomas Jefferson Medical College, Philadelphia, PA 19107, USA

Copyright © 2001 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


We investigated the role of apoptosis in the development of B cell memory by analyzing thep-azophenylarsonate Ars response in a line of A strain mice in which expression of humanBcl-2 was enforced in the B cell compartment. Previous studies of the Ars immune response inthese A. Bcl-2 mice, demonstrated that a large percentage of the antibodies expressed by the Arsinduced memory B cell compartment had accumulated point mutations via somatic hypermutationthat increased their affinity for both Ars and the autoantigen DNA -dual reactive- antibodies.This was in sharp contrast to normal A strain mice which displayed no dual reactive B cellsin their Ars induced memory B cell compartment. These data suggested that interference withapoptotic pathways regulated by Bcl-2 allows developing memory B cells that have acquiredautoreactivity to bypass a peripheral tolerance checkpoint. Further studies of these mice,reported here, demonstrate that enforced expression of Bcl-2 does not alter serum antibodyaffinity maturation nor positive selection of B cells expressing somatically mutated antibodywith an increased affinity for Ars. Moreover, the somatic hypermutation process was unaffectedin A. Bcl-2 mice. Thus, enforced expression of Bcl-2 in A. Bcl-2 mice appears to selectivelyalter a negative selection process that operates during memory B cell differentiation.

Author: Evangelia Notidis, Shailaja Hande, and Tim Manser

Source: https://www.hindawi.com/


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