Effect of cell: Cell competition and BAFF expression on peripheral B cell tolerance and B-1 cell survival in transgenic mice expressing a low level of Igκ-reactive macroself antigen

Abstract

In mice carrying a synthetic Igκ-reactive superantigen ("κ macroself antigen"), low level expression induced split peripheral B cell tolerance in the sIgκ+ compartment, with striking reductions in follicular and marginal zone (MZ) B cells and the retention of significant numbers of sIgκ + B-1a but not B-1b cells in the peritoneum. Here, we characterize the transgenic line pKκ with this split tolerance phenotype and assess the effects of B cell competition and the survival cytokine BAFF (B cell activating factor belonging to the TNF family) on peripheral tolerance. In pKκ mice the surviving peritoneal and splenic κ+ B cells were largely lost in mice carrying one copy of the human Cκ exon in place of the mouse version, a maneuver that generates additional antigen non-reactive competitor B cells in this model. Furthermore, overexpression of BAFF suppressed κ-macroself antigen-induced deletion and promoted production of both IgM,κ and IgA,κ antibodies in mice with normal Igκ alleles but not in mice carrying one copy of the human Cκ allele. These findings suggest that BAFF overexpression has minimal effects on the survival of autoreactive B cells in a polyclonal immune system and that B cell:B cell competition plays a potent role in suppressing the survival of B-1 and splenic B cells with excessive autoreactivity. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.