Impaired affinity maturation in Cr2-/- mice is rescued by adjuvants without improvement in germinal center development.
Cr2-/- mice have an impairment in humoral immunity, as shown by the decrease in the Ab titers against T cell-dependent Ags and abnormalities in germinal center formation. Germinal centers are present, but they are decreased in size and number, indicating problems in their development. In this study, we investigated whether this abnormality in germinal center development is associated with problems in the establishment of optimal affinity maturation and the generation of memory B cells, processes closely related to the germinal center reaction. We immunized the Cr2-/- animals with different Ags with or without adjuvants. We showed that, when immunized without adjuvants, complement receptors are absolutely required for optimal affinity maturation. Although limited affinity maturation is elicited in the Cr2-/- Ab response, it is decreased as compared with normal animals. Memory B cell generation is also impaired. In the presence of adjuvants, germinal center development in the Cr2-/- mice is still abnormal, as demonstrated by their decreased size and number. Surprisingly, adjuvants establish optimal affinity maturation and partially restore the amount of Ab produced during the primary response and memory B cell generation. However, adjuvants cannot improve the ability of follicular dendritic cells to retain Ags in the form of immune complexes. These observations indicate that immunization with inflammatory Ags offset some of the immunological abnormalities found in the Cr2-/- mice and show that optimal affinity maturation in the Cr2-/- mice can be achieved in the absence of normal germinal centers.
Wu
X
X
Division of Rheumatology, Department of Medicine, and Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jiang
N
N
Fang
Y F
YF
Xu
C
C
Mao
D
D
Singh
J
J
Fu
Y X
YX
Molina
H
H
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000534:Alum Compounds; D000818:Animals; D000915:Antibody Affinity / Q000235:genetics*; D000941:Antigens / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000378:metabolism; D018858:Germinal Center / Q000276:immunology* / Q000473:pathology*; D006241:Haptens / Q000378:metabolism; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000517:prevention & control; D007156:Immunologic Memory / Q000235:genetics; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D009596:Nitrophenols / Q000378:metabolism; D010648:Phenylacetates; D017464:Receptors, Complement 3d / Q000172:deficiency* / Q000235:genetics*; D013154:Spleen / Q000033:anatomy & histology / Q000276:immunology / Q000378:metabolism
C098951:4-hydroxy-3-nitrophenylacetyl-keyhole limpet hemocyanin; D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000941:Antigens; D006241:Haptens; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009596:Nitrophenols; D010648:Phenylacetates; D017464:Receptors, Complement 3d; C026242:4-hydroxy-5-nitrophenyl acetic acid; C041524:aluminum sulfate; D006433:Hemocyanins