title: Efficient generation of B lymphocytes by recognition of self-antigens.
abstract: Antibody diversity is generated by a random gene recombination process with the inherent risk of the production of autoreactive specificities. The current view suggests that B cells expressing such specificities are negatively selected at an early developmental stage. Using the knock-in model system of the 3-83 autoreactive B-cell antigen receptor (BCR) in combination with precursor-BCR (pre-BCR) deficiency, we show here that the 3-83 BCR mediates efficient generation of B cells in the presence, but not the absence, of a strongly recognized auto-antigen. Experiments with mixed bone marrow chimeras showed that combining the 3-83 BCR with the corresponding auto-antigen resulted in efficient reconstitution of B-cell development in immune-deficient mice. These results suggest that B cells are positively selected by recognition of self-antigens during developmental stages that precede receptor editing. Moreover, the data indicate that the pre-BCR functions as a specialized autoreactive BCR to initiate positive selection at a stage where the cells express immunoglobulin heavy but not light chains.
authors: Center for Biological Signalling Studies, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors: Cathrin
authors: C
authors: Eschbach
authors: Martina P
authors: MP
authors: Bach
authors: Ingrid
authors: I
authors: Fidler
authors: Roberta
authors: R
authors: Pelanda
authors: Fabian
authors: F
authors: Köhler
authors: Klaus
authors: K
authors: Rajewsky
authors: Hassan
authors: H
authors: Jumaa
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