Uncoupling CD21 and CD19 of the B-cell coreceptor.
Complement receptors (CRs) CD21 and CD35 form a coreceptor with CD19 and CD81 on murine B cells that when coligated with the B-cell receptor lowers the threshold of activation by several orders of magnitude. This intrinsic signaling role is thought to explain the impaired humoral immunity of mice bearing deficiency in CRs. However, CRs have additional roles on B cells independent of CD19, such as transport of C3-coated immune complexes and regulation of C4 and C3 convertase. To test whether association of CR with CD19 is necessary for their intrinsic activation-enhancing role, knockin mice expressing mutant receptors, Cr2(Delta/Deltagfp), that bind C3 ligands but do not signal through CD19 were constructed. We found that uncoupling of CR and CD19 significantly diminishes survival of germinal center B cells and secondary antibody titers. However, B memory is less impaired relative to mice bearing a complete deficiency in CRs on B cells. These findings confirm the importance of interaction of CR and CD19 for coreceptor activity in humoral immunity but identify a role for CR in B-cell memory independent of CD19.
Barrington
Robert A
RA
The Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
Schneider
Thomas J
TJ
Pitcher
Lisa A
LA
Mempel
Thorsten R
TR
Ma
Minghe
M
Barteneva
Natasha S
NS
Carroll
Michael C
MC
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007114:Immunization; D007156:Immunologic Memory / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D017463:Receptors, Complement 3b / Q000235:genetics / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism
C098951:4-hydroxy-3-nitrophenylacetyl-keyhole limpet hemocyanin; D018941:Antigens, CD19; D006241:Haptens; D018398:Homeodomain Proteins; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; C064658:RAG-1 protein; D049452:Green Fluorescent Proteins; D006433:Hemocyanins
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