B-1 cell development: evidence for an uncommitted immunoglobulin (Ig)M+ B cell precursor in B-1 cell differentiation.
Murine phosphatidyl choline (PtC)-specific B cells in normal mice belong exclusively to the B-1 subset. Analysis of anti-PtC (VH12 and VH12/Vkappa4) transgenic (Tg) mice indicates that exclusion from B-0 (also known as B-2) occurs after immunoglobulin gene rearrangement. This predicts that PtC-specific B-0 cells are generated, but subsequently eliminated by either apoptosis or differentiation to B-1. To investigate the mechanism of exclusion, PtC-specific B cell differentiation was examined in mice expressing the X-linked immunodeficiency (xid) mutation. xid mice lack functional Bruton's tyrosine kinase (Btk), a component of the B cell receptor signal transduction pathway, and are deficient in B-1 cell development. We find in C57BL/ 6.xid mice that VH12 pre-BII cell selection is normal and that PtC-specific B cells undergo modest clonal expansion. However, the majority of splenic PtC-specific B cells in anti-PtC Tg/xid mice are B-0, rather than B-1 as in their non-xid counterparts. These data indicate that PtC-specific B-0 cell generation precedes segregation as predicted, and that Btk function is required for efficient segregation to B-1. Since xid mice exhibit defective B cell differentiation, not programmed cell death, these data are most consistent with an inability of PtC-specific B-0 cells to convert to B-1 and a single B cell lineage.
Clarke
S H
SH
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. shl@med.unc.edu
Arnold
L W
LW
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage; D015322:Gene Rearrangement, B-Lymphocyte; D008040:Genetic Linkage; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D007154:Immune System Diseases / Q000235:genetics; D007075:Immunoglobulin M; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010537:Peritoneum / Q000276:immunology; D010713:Phosphatidylcholines / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D012729:Sex Chromosome Aberrations; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014960:X Chromosome
D001324:Autoantigens; D007075:Immunoglobulin M; D010713:Phosphatidylcholines; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse