Mm. Rosado et Aa. Freitas, B cell positive selection by self antigens and counter-selection of dual Bcell receptor cells in the peripheral B cell pools, EUR J IMMUN, 30(8), 2000, pp. 2181-2190
The presence of B cells expressing two B cell receptors (BCR), described in
BCR-transgenic, gene-targeted and normal mice, may represent an autoimmune
hazard. We generated RAG-2-deficient mice bearing two complete rearranged
immunoglobulin transgenes. In these mice most mature resting B cells expres
s chains from the two transgenes. We studied selection of these dual recept
or B cells in the presence of self antigens. In spite of the reduced surfac
e density of the anti-self receptor, self-reactive B cells are deleted in t
he presence of membrane-bound self antigens. In contrast, the presence of s
oluble self antigen positively selects single receptor B cells expressing t
he self-reactive receptor. At the periphery these positively selected B cel
ls down-regulate surface IgM expression and become unresponsive. A few dual
receptor cells, however, escape tolerance induction. We examined the perip
heral fate of the dual receptor B cells and showed that they are poorly sel
ected into the activated B cell compartment and show a poor competitive cap
acity when in presence of populations of single receptor B cells. These res
ults indicate that peripheral selection contributes to the very low frequen
cies of dual receptor B cells in normal mice and that multiple safeguard me
chanisms operate to minimize the autoimmune hazard that allelically include
d B cells could represent.