title: 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.
authors.affiliation: Department of Immunology, Bruce Rappaport Faculty of Medicine and Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Shoham
authors.initials: S
authors.lastname: Shivtiel
authors.forename: Nira
authors.initials: N
authors.lastname: Leider
authors.forename: Doron
authors.initials: D
authors.lastname: Melamed
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D001324:Autoantigens / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*
chemical_list: D001324:Autoantigens; D011947:Receptors, Antigen, B-Cell; D017493:Leukocyte Common Antigens