Migration and differentiation of autoreactive B-1 cells induced by activated gamma/delta T cells in antierythrocyte immunoglobulin transgenic mice

Using normal and transgenic (Tg) mice, we have shown that peritoneal B-1 ce lls are activated by administration of cytokines or lipopolysaccharide and migrate to other lymphoid organs where they differentiate into antibody-sec reting cells. However, little is known about the process of B-1 cell migrat ion and differentiation in vivo. We developed a mouse line by crossing the antierythrocyte antibody Tg mice (HL mice) with TCR-gamma/delta Tg mice spe cific for a self-thymus leukemia (TL) antigen in the recombination activati ng gene (RAG)2(-/-) background. In the presence of the self-antigen, Tg gam ma/delta T cells increased in number and manifested activated phenotypes. P eritoneal B-1 cells in these mice migrated into mesenteric lymph nodes and differentiated into autoantibody-secreting cells, resulting in strong autoi mmune hemolytic anemia. Furthermore, transfer of RAG2(-/-) X HL bone marrow or peritoneal cells into the peritoneal cavity of RAG2(-/-) X TCR-gamma/de lta Tg mice gave rise to donor-derived B-1 cells in mesenteric lymph nodes, and these cells produced the autoantibody. Thus, this study demonstrates t hat the migration of B-1 cells and differentiation into the antibody-secret ing cells can be induced by noncognate T cell help and implies the possibil ity that gamma/delta T cells may induce B-1 cell differentiation in vivo.