Migration and Differentiation of Autoreactive B-1 Cells Induced by Activated γ/δ T Cells in Antierythrocyte Immunoglobulin Transgenic Mice

Using normal and transgenic (Tg) mice, we have shown that peritoneal B-1 cells are activated by administration of cytokines or lipopolysaccharide and migrate to other lymphoid organs where they differentiate into antibody-secreting cells. However, little is known about the process of B-1 cell migration and differentiation in vivo. We developed a mouse line by crossing the antierythrocyte antibody Tg mice (HL mice) with TCR-γ/δ Tg mice specific for a self-thymus leukemia (TL) antigen in the recombination activating gene (RAG)2^−/− background. In the presence of the self-antigen, Tg γ/δ T cells increased in number and manifested activated phenotypes. Peritoneal B-1 cells in these mice migrated into mesenteric lymph nodes and differentiated into autoantibody-secreting cells, resulting in strong autoimmune hemolytic anemia. Furthermore, transfer of RAG2^−/− × HL bone marrow or peritoneal cells into the peritoneal cavity of RAG2^−/− × TCR-γ/δ Tg mice gave rise to donor-derived B-1 cells in mesenteric lymph nodes, and these cells produced the autoantibody. Thus, this study demonstrates that the migration of B-1 cells and differentiation into the antibody-secreting cells can be induced by noncognate T cell help and implies the possibility that γ/δ T cells may induce B-1 cell differentiation in vivo.