Antibody reactivity to self-antigens is a normal component of the immune system. To study the mechanism by which self-reactive B cells are generated and maintained, we analyzed a cell development in transgenic mice that express a rearranged V(H)81X heavy chain from the pre-immune repertoire. In these mice, > 95% of B cells express the transgene in association with a variety of kappa light chains but V(κ)1C being the dominant light chain. These transgenic a cells with identical V(κ)1C-J(κ)5 joins do not normally secrete IgM in vivo but antibodies derived from these a cells, through LPS activation in vitro or after hybridoma immortalization, are self-reactive and recognize an ubiquitous epitope(s) on intracytoplasmic proteins from different tissues. They 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(κ)1CJ(κ) IgM antibody. The observations in this transgenic mouse provide evidence for positive selection of a population of self-reactive a cells. These B cells enter the peripheral pool of B cells where they localize in the marginal zone of the spleen and, in contrast to other transgene-expressing B cells, do not secrete IgM antibody.