Expression of human complement receptor type 2 (CD21) in mice during early B cell development results in a reduction in mature B cells and hypogammaglobulinemia.
Complement receptor (CR) type 2 (CR2/CD21) is normally expressed only during the immature and mature stages of B cell development. In association with CD19, CR2 plays an important role in enhancing mature B cell responses to foreign Ag. We used a murine Vlambda2 promoter/Vlambda2-4 enhancer minigene to develop transgenic mice that initiate expression of human CR2 (hCR2) during the CD43(+)CD25(-) late pro-B cell stage of development. We found peripheral blood B cell numbers reduced by 60% in mice expressing high levels of hCR2 and by 15% in mice with intermediate receptor expression. Splenic B cell populations were altered with an expansion of marginal zone cells, and basal serum IgG levels as well as T-dependent immune responses were also significantly decreased in transgenic mice. Mice expressing the highest levels of hCR2 demonstrated in the bone marrow a slight increase in B220(int)CD43(+)CD25(-) B cells in association with a substantial decrease in immature and mature B cells, indicative of a developmental block in the pro-B cell stage. These data demonstrate that stage-specific expression of CR2 is necessary for normal B cell development, as premature receptor expression substantially alters this process. Alterations in B cell development are most likely due to engagement of pre-B cell receptor-mediated or other regulatory pathways by hCR2 in a CD19- and possibly C3 ligand-dependent manner.
Marchbank
Kevin J
KJ
Complement Biology Group, Department of Medical Biochemistry, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom.
Kulik
Liudmila
L
Gipson
Matthew G
MG
Morgan
B Paul
BP
Holers
V Michael
VM
D000361:Agammaglobulinemia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D016130:Immunophenotyping; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D017464:Receptors, Complement 3d / Q000096:biosynthesis* / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D007074:Immunoglobulin G; D017464:Receptors, Complement 3d