Rapid elimination of mature autoreactive B cells demonstrated by Cre-induced change in B cell antigen receptor specificity in vivo

Rapid elimination of mature autoreactive B cells demonstrated by Cre-induced change in B cell antigen receptor specificity in vivo

Kong-Peng Lam* and
Klaus Rajewsky

Institute for Genetics, University of Cologne, Weyertal 121, D-50931 Cologne, Germany

Contributed by Klaus Rajewsky

Abstract

Developing autoreactive B cells edit their B cell antigen receptor (BCR) in the bone marrow and are clonally deleted when they fail to reexpress an innocent BCR. Here, inducible Cre-loxP-mediated gene inversion is used to change the specificity of the BCR on mature IgM⁺ IgD⁺ B cells in vivo to address the fate of lymphocytes encountering self-antigens at this developmental stage. Expression of an autoreactive BCR on mature B cells leads to their rapid elimination from the periphery, a process that is inhibited by constitutive bcl-2 transgene expression in an antigen dose-dependent manner. Thus, selection of mature B cells into the long-lived peripheral pool does not prevent their deletion upon encounter of self-antigens.

Footnotes

↵ * To whom reprint requests should be addressed at the present address: Institute of Molecular and Cell Biology, The National University of Singapore, 30 Medical Drive, S117609, Republic of Singapore. e-mail: mcblamkp{at}imcb.nus.edu.sg.
ABBREVIATIONS:

BCR,

B cell antigen receptor;

H,

heavy;

L,

light;

V,

variable;

Dtg,

3–83B1–8f/+, 3–83ki/+;

IFN,

interferon;

tg,

transgene;

Id,

idiotype