Humoral immune responses in Cr2-/- mice: enhanced affinity maturation but impaired antibody persistence.
Deficiency in CD21/CD35 by disruption of the Cr2 loci leads to impaired humoral immune responses. In this study, we detail the role of CD21/CD35 on Ab responses to the hapten (4-hydroxy-3-nitrophenyl)acetyl conjugated to chicken gamma-globulin. Surprisingly, Cr2-/- mice generate significant Ab responses and germinal center (GC) reactions to low doses of this Ag in alum, although the magnitude of their responses is much reduced in comparison with those of Cr2+/- and C57BL/6 controls. Increasing Ag dose partially corrected this deficit. In situ study of the somatic genetics of GC B cells demonstrated that VDJ hypermutation does not require CD21/CD35, and Cr2-/- mice exhibited enhanced affinity maturation of serum Ab in the post-GC phase of the primary response. On the other hand, Cr2-/- mice displayed accelerated loss of serum Ab and long-lived Ab-forming cells. These observations suggest that B cell activation/survival signals mediated by CD21 and/or the retention of Ag by CD21/CD35 play important roles in the generation, quality, and maintenance of serum Ab.
Chen
Z
Z
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Koralov
S B
SB
Gendelman
M
M
Carroll
M C
MC
Kelsoe
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity / Q000235:genetics*; D000921:Antibody-Producing Cells / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D001666:Binding Sites, Antibody / Q000235:genetics*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002645:Chickens; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010648:Phenylacetates; D017463:Receptors, Complement 3b / Q000172:deficiency / Q000235:genetics; D017464:Receptors, Complement 3d / Q000172:deficiency / Q000235:genetics* / Q000276:immunology*; D005719:gamma-Globulins / Q000008:administration & dosage / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D009596:Nitrophenols; D010648:Phenylacetates; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D005719:gamma-Globulins; C026242:4-hydroxy-5-nitrophenyl acetic acid