Germinal center-associated nuclear protein contributes to affinity maturation of B cell antigen receptor in T cell-dependent responses.
Acquired immunity depends on proliferation and differentiation of antigen (Ag)-specific B cells in germinal centers (GCs) of lymphoid follicles in response to T cell-dependent Ags. Here, we studied the function of GC-associated nuclear protein that is selectively up-regulated in GC-B cells. B cell-specific ganp-deficient mice were compromised in affinity maturation of hapten-specific antibodies against T cell-dependent Ags with retarded development of GCs. B cell numbers and development, serum Ig levels, mitogen-induced B cell proliferation in vitro, and responses to T cell-independent Ag were nearly normal; however, the mutant B cells showed a decrease in anti-CD40-induced proliferation and an increased susceptibility to B cell apoptosis in vitro and in vivo. B cell-specific ganp-deficient mice showed a decreased frequency of variable-region somatic mutations, especially of the high-affinity type (W(33) --> L) in the V(H)186.2 region against nitrophenyl-chicken gamma globulin, whereas the class switching was normal. We conclude that GC-associated nuclear protein is necessary for generation or maintenance of B cells with high-affinity B cell Ag receptors during the maturation in GCs.
Kuwahara
Kazuhiko
K
Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto 860-8556, Japan.
Fujimura
Satoru
S
Takahashi
Yoshimasa
Y
Nakagata
Naomi
N
Takemori
Toshitada
T
Aizawa
Shinichi
S
Sakaguchi
Nobuo
N
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D017931:DNA Primers; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D017931:DNA Primers; C481510:GANP protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell