Receptor editing in CD45-deficient immature B cells.

Abstract

B cell receptor signaling threshold regulates negative selection of autoreactive B cells and determines the mechanism of B cell tolerance. Using mice carrying immunoglobulin transgene specific for MHC class I antigen K(k) (3-83 Tg mice), and IL-7-driven bone marrow (BM) culture system, we have previously shown that receptor editing is a major mechanism in B cell tolerance. To test the role of BCR signaling competence on the induction of tolerance-mediated receptor editing, we crossed the 3-83 Tg mice with mice deficient in CD45, a protein tyrosine phosphatase that functions asa positive regulator of the BCR signaling. We found that in the absence of self-antigen allelic exclusion is efficiently imposed in 3-83 Tg CD45(-/-) mice, although numbers of peripheral B cells are reduced. Using our BM culture system, we show here that immature 3-83 Tg CD45(-/-) B cells encountering self-antigen are developmentally arrested and undergo secondary light chain recombination and receptor editing, not different than CD45-sufficient cells. Thus, lack of CD45 does not abolish the receptor editing competence in immature B cells encountering high avidity membrane-bound antigen.