Generation, expansion, migration and activation of mouse B1 cells.
We have studied the expansion, activation, homing and antibody production of B1 cells in two different mouse models. One is the HL transgenic mouse, which carries Ig genes encoding the anti-red blood cell autoantibody (4C8) and develops autoimmune hemolytic anemia by the activation of autoreactive B1 cells that escape from clonal deletion and expand in the peritoneal cavity (PEC). The other model is represented by alymphoplasia (aly) mice, which carry a point mutation in the gene encoding NF-kappaB-inducing kinase (NIK) and have drastically reduced immunoglobulin serum levels, in spite of their peritoneal cavity containing a large number of B1 cells. We have found that a) expression levels of the B-cell antigen receptor (BCR) influence the size of the B1 -cell compartment and efficiency of allelic exclusion and B2-cell deletion; b) antibody production of B1 cells is closely related with their migration from PEC to other lymphoid organs and is dependent on NIK; and c) infection, lipopolysaccharide stimulation, cytokine administration or T-cell activation by noncanonical antigens induces migration and differentiation of peritoneal B1 cells into antibody-producing cells. We describe a scenario where most of B1 and B2 differences are due to a distinct activation threshold of BCR and antigen repertoire.
Fagarasan
S
S
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Yoshida, Japan.
Watanabe
N
N
Honjo
T
T
D000744:Anemia, Hemolytic, Autoimmune / Q000235:genetics / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D002455:Cell Division; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D004912:Erythrocytes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008954:Models, Biological; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology
D001323:Autoantibodies; D016692:Receptors, Antigen, T-Cell, gamma-delta