CD5 maintains tolerance in anergic B cells.
Clonal anergy of autoreactive B cells is a key mechanism regulating tolerance. Here, we show that anergic B cells express significant surface levels of CD5, a molecule normally found on T cells and a subset of B-1 cells. Breeding of the hen egg lysozyme (HEL) transgenic model for B cell anergy onto the CD5 null background resulted in a spontaneous loss of B cell tolerance in vivo. Evidence for this included elevated levels of anti-HEL immunoglobulin M (IgM) antibodies in the serum of CD5(-/-) mice transgenic for both an HEL-specific B cell receptor (BCR) and soluble lysozyme. "Anergic" B cells lacking CD5 also showed enhanced proliferative responses in vitro and elevated intracellular Ca(2+) levels at rest and after IgM cross-linking. These data support the hypothesis that CD5 negatively regulates Ig receptor signaling in anergic B cells and functions to inhibit autoimmune B cell responses.
Hippen
K L
KL
Center for Immunology, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA. keli.l.hippen-1@tc.umn.edu
Tze
L E
LE
Behrens
T W
TW
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000235:genetics*; D020013:Calcium Signaling; D017635:Clonal Anergy; D007152:Immunologic Capping; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics; D011947:Receptors, Antigen, B-Cell
D018956:CD5 Antigens; D011947:Receptors, Antigen, B-Cell; D009113:Muramidase