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PMID: 9547343 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

B-1 cell development: evidence for an uncommitted immunoglobulin (Ig)M+ B cell precursor in B-1 cell differentiation.

The Journal of experimental medicine ·Vol. 187 ·No. 8 ·1998-04-20 ·Pages 1325-34

Clarke SH, Arnold LW

Abstract

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.

MeSH Terms
Agammaglobulinaemia Tyrosine Kinase Animals Autoantigens/immunology B-Lymphocyte Subsets/cytology,immunology Bone Marrow/immunology Cell Differentiation Cell Lineage Gene Rearrangement, B-Lymphocyte Genetic Linkage Hematopoietic Stem Cells/cytology,immunology Immune System Diseases/genetics Immunoglobulin M Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Mutant Strains Peritoneum/immunology Phosphatidylcholines/immunology Protein-Tyrosine Kinases/genetics Sex Chromosome Aberrations Spleen/cytology,immunology X Chromosome
Chemicals
Autoantigens Immunoglobulin M Phosphatidylcholines Protein-Tyrosine Kinases Agammaglobulinaemia Tyrosine Kinase Btk protein, mouse
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Clarke S H
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
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.187.8.1325
Email
shl@med.unc.edu
Published
1998-04-20
Pages
1325-34
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2212222
Subset
IM
Grants
NIAID NIH HHS · AI-29576 · United States
NIAMS NIH HHS · AR-42573 · United States
External Links
PubMed source DOI: 10.1084/jem.187.8.1325 PMC Full Text View journal details
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