Identification of a precursor to phosphatidyl choline-specific B-1 cells suggesting that B-1 cells differentiate from splenic conventional B cells in vivo: cyclosporin A blocks differentiation to B-1.
The origin of B-1 cells is controversial. The initial paradigm posited that B-1 and B-2 cells derive from separate lineages. More recently it has been argued that B-1 cells derive from conventional B cells as a result of T-independent Ag activation. To understand B-1 cell differentiation, we have generated Ig transgenic (Tg) mice using the H and L chain genes (VH12 and Vkappa4) of anti-phosphatidyl choline (anti-PtC) B cells. In normal mice anti-PtC B cells segregate to B-1. Segregation is intact in VH12 (6-1) and VH12/Vkappa4 (double) Tg mice that develop large numbers of PtC-specific B cells. However, if B-1 cell differentiation is blocked, anti-PtC B cells in these Tg mice are B-2-like in phenotype, suggesting the existence of an Ag-driven differentiative pathway from B-2 to B-1. In this study, we show that double Tg mice have a population of anti-PtC B cells that have the phenotypic characteristics of both B-2 and B-1 cells and that have the potential to differentiate to B-1 (B-1a and B-1b). Cyclosporin A blocks this differentiation and induces a more B-2-like phenotype in these cells. These findings indicate that these cells are intermediate between B-2 and B-1, further evidence of a B-2 to B-1 differentiative pathway.
Arnold
L W
LW
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
McCray
S K
SK
Tatu
C
C
Clarke
S H
SH
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D006131:Growth Inhibitors / Q000494:pharmacology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010713:Phosphatidylcholines / Q000276:immunology*; D013154:Spleen / Q000166:cytology* / Q000276:immunology / Q000637:transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*
D018985:Epitopes, B-Lymphocyte; D006131:Growth Inhibitors; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D010713:Phosphatidylcholines; D016572:Cyclosporine