Expression levels of B cell surface immunoglobulin regulate efficiency of allelic exclusion and size of autoreactive B-1 cell compartment

Surface-expressed immunoglobulin (Ig) has been shown to have a critical rol e in allelic exclusion of Ig heavy (H) and light (L) chains. Although vario us degrees of suppression of endogenous Ig expression are observed in Ig tr ansgenic (Tg) mice, it was not clear whether this difference is due to diff erent onsets of Tg expression or to different levels of Tg expression, whic h are obviously affected by integration sites of the transgene. In this stu dy we generated antierythrocyte antibody Tg mice that carry tandem joined H and L chain transgenes (H+L) and confirmed that homozygosity of the transg ene loci enhances the level of transgene expression as compared with hetero zygosity. Suppression of endogenous H and L chain gene expression was stron ger in homozygous than in heterozygous Tg mice. Similar results were obtain ed in control Tg mice carrying the H chain only. These results suggest that there is a threshold of the B cell receptor expression level that induces allelic exclusion. In addition, despite the same B cell receptor specificit y, the size of Tg autoreactive B-1 cell compartment in the peritoneal cavit y is larger in homozygous than in heterozygous mice, although the number of the Tg B-2 cell subset decreased in the spleen and bone marrow of homozygo us Tg mice as compared with heterozygous Tg mice. By contrast, homozygosity of the H chain alone Tg line, which does not recognize self-antigens, did not increase the size of the peritoneal B-1 subset. These results suggest t hat the size of the B-1 cell subset in the Tg mice may depend on strength o f signals through B cell receptors triggered by self-antigens.