EVIDENCE FOR SELECTION OF A POPULATION OF MULTI-REACTIVE B-CELLS INTOTHE SPLENIC MARGINAL ZONE

Antibody reactivity to self-antigens is a normal component of the immu ne system. To study the mechanism by which self-reactive B cells are g enerated and maintained, we analyzed B cell development in transgenic mice that express a rearranged V(H)81X heavy chain from the preimmune repertoire, In these mice, >95% of B cells express the transgene in as sociation with a variety of kappa light chains but V(kappa)1C being th e dominant light chain, These transgenic B cells with identical V(kapp a)1C-J(kappa)5 joins do not normally secrete IgM in vivo, but antibodi es derived from these a cells, through LPS activation in vitro or afte r hybridoma immortalization, are self-reactive and recognize an ubiqui tous epitope(s) on intracytoplasmic proteins from different tissues. T hey have the phenotype and localization pattern of long-lived marginal zone a cells and their development in vivo is blocked by injection of soluble V(H)81X-V(kappa)1CJ(kappa)5 IgM antibody, The observations in this transgenic mouse provide evidence for positive selection of a po pulation of self-reactive B cells. These B cells enter the peripheral pool of a cells where they localize in the marginal zone of the spleen and, in contrast to other transgene-expressing B cells, do not secret e IgM antibody.