Accumulation of somatic hypermutation and antigen-driven selection in rapidly cycling surface Ig+ germinal center (GC) B cells which occupy GC at a high frequency during the primary anti-hapten response in mice.
Well-developed germinal centers (GC) contain rapidly dividing surface immunoglobulin-negative (sIg-) B cells (centroblasts), and most of their progeny are sIg+ B cells (centrocytes) in a resting state. It has been predicted that somatic hypermutation occurs in centroblasts, whereas antigen-driven selection takes place in centrocytes. The present analysis indicates that murine GC B cells bearing sIg with specificity for an immunizing antigen are in a rapidly cycling state and increase exponentially in number to occupy spleen GC at high frequency during the 1st week after primary immunization; however, the number of these cells is significantly reduced in the 2nd week of immunization. During that period, these proliferating sIg+ GC B cells accumulate somatic hypermutations with nucleotide exchanges indicative of affinity maturation. These sIg+ GC B cells co-express B7-2, ICAM-1, and LFA-1, and have potent antigen-presenting activity which results in T cell activation in vitro. These observations indicate that the sIg+ GC B cells accumulate somatic hypermutations and undergo antigen-driven selection through proliferation, probably upon activation by T cells. This sIg+ GC B cell population may represent cell cycling centrocytes; however, the possibility that these may represent centroblasts undergoing re-expression of sIg could not be excluded.
Kimoto
H
H
Department of Immunology, NIH of Japan, Tokyo.
Nagaoka
H
H
Adachi
Y
Y
Mizuochi
T
T
Azuma
T
T
Yagi
T
T
Sata
T
T
Yonehara
S
S
Tsunetsugu-Yokota
Y
Y
Taniguchi
M
M
Takemori
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000916:Antibody Diversity; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology*; D017209:Apoptosis; D001483:Base Sequence; D002453:Cell Cycle; D005260:Female; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology; D006241:Haptens / Q000276:immunology; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000941:Antigens; D006241:Haptens; D011947:Receptors, Antigen, B-Cell; D017493:Leukocyte Common Antigens