Previous studies have suggested peritoneal B-1a cells play a vital role in the development of anti-erythrocyte antibodies (AEA), but this remains controversial. While studying the Lbw2 lupus-susceptibility locus on chr 4, we discovered a subcongenic line, Lbw2-SE (NZB strain with 20 Mb NZW), that was deficient in peritoneal B-1a cells. NZB mice spontaneously develop autoimmune hemolytic anemia (AIHA) and exhibit an expansion of peritoneal B-1a cells, therefore we used this congenic to study the role of B-1a B cells in AEA production. Compared to NZB, Lbw2-SE mice had decreased total number of peritoneal B cell subsets (B-1a, B-1b, and B-2) but no differences in the number of splenic B cell subsets and a slight delay in AEA incidence similar to Lbw-2 congenics. To precisely map the B-1a-affecting variant, additional subcongenics were generated of which two (SEA & SED) had the low B1a phenotype. They, however, did not overlap suggesting the responsible mutation was located outside of the Lbw2-SE interval. The SEA and SED sublines had AIHA similar to NZB mice, while the SEB and SEC sublines had normal numbers of B-1a cells yet lower incidences of AIHA. Interestingly, after administering a TLR3 agonist to induce AEAs in young mice, the SEA and SED sublines with fewer B-1a cells demonstrated resistance to the development of AEAs. Our data indicate that B-1a cells are not required for the development of AEAs, but can enhance induction of AIHA under environmental conditions.
- Copyright © 2013 by The American Association of Immunologists, Inc.