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 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-gamma/delta 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 gamma/delta 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(-/-) x HL bone marrow or peritoneal cells into the peritoneal cavity of RAG2(-/-) x TCR-gamma/delta 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 gamma/delta T cells may induce B-1 cell differentiation in vivo.
Watanabe
N
N
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Ikuta
K
K
Fagarasan
S
S
Yazumi
S
S
Chiba
T
T
Honjo
T
T
D000740:Anemia / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D006239:Haplotypes; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008643:Mesentery; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010529:Peritoneal Cavity / Q000166:cytology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D001323:Autoantibodies; D004268:DNA-Binding Proteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D007136:Immunoglobulins; C499308:Rag2 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; C064655:V(D)J recombination activating protein 2; D017493:Leukocyte Common Antigens