A transgenic model of autoimmune hemolytic anemia.

Abstract

SummaryWe made double transgenic mice bearing immunoglobulin heavy and light chain genes encoding an autoantibody against the mouse erythrocyte by the cross of C57BL/6 mice carrying the transgene for each chain of the immunoglobulin. Although no obvious disorders were found in the singlechain transgenic mice, severely anemic symptoms were found in some of the double transgenic mice, in which most B cells express, at least on their surface, the autoantibody reactive to selfantigens on the erythrocyte. Individual double-transgenic mice showed a wide variation of phenotypes between severe anemia and no symptoms. Both deletion and anergy of autoreactive B cells were seen in each individual mouse, but their relative contribution to self-tolerance was variable and not directly related to the severity of anemia or the amount of the autoantibody produced. This transgenic system provides a good autoimmune disease model for exploring its onset mechanism, and means of its treatment and prevention.

Humoral Autoimmunity to Basement Membrane Antigens Is Regulated in C57BL/6 and MRL/MpJ Mice Transgenic for Anti-Laminin Ig Receptors

“…Although a modest decrease in splenic B cells attributed to a shortened half-life of anergic B cells is reported in some anergizing models (35,39,40), the 8-fold decrease in B cell number observed in LamH-C Tg ϩ mice best mirrors the dramatic hypocellularity reported in other model systems in which deletion is a dominant mechanism of tolerance (16,21,41,42), and contrasts with the near-normal number of B cells observed in mice Tg for an Ig reactive with foreign Ag (38,43). This suggests that a large subset of B cells bearing LamH-C H chain/endogenous L chain combinations engage self-Ag in a manner that qualitatively and/or quantitatively is sufficient to promote clonal deletion.…”

Preferential Localization of Human CD5+ B Cells in the Peritoneal Cavity

“…Murine CD5 þ B cells constitute about 60% of peritoneal B cells, but only less than 2% of B cells in spleens and lymph nodes [2,3,14]. We have shown that murine B-1 cells play pivotal roles in the induction of autoimmune haemolytic anaemia in anti-erythrocyte immunoglobulin transgenic mice [15,16]. Peritoneal B-1 cells of these transgenic mice are shown to be activated by bacterial environmental antigens and to produce anti-erythrocyte autoantibodies, triggering autoimmune haemolytic anaemia.…”

B Cells Expressing a Natural Polyreactive Autoantibody Have a Distinct Phenotype and Are Overrepresented in Immunoglobulin Heavy Chain Transgenic Mice

“…Previous studies of Ig tg mice have demonstrated that segregation of B cell populations is dictated by BCR specificity in that B cells expressing B1-derived BCR develop into B1 cells whereas B cells expressing B2-derived BCR become B2 cells (39,45,63,75). However, recent studies have shown that BCR signal strength plays an important role in deciding B cell fate.…”