Analysis of antigen-stimulated B cell migration into germinal centers during the early stage of a T-dependent immune response.
The quasimonoclonal (QM) mouse provides a model to analyze B cell selection because major B cell antigen receptors (BCR) are composed of the knockin V(H)DJ(H) 17.2.25 (V(H)T) encoded H chain and the lambda1 or lambda2 L chain, thereby being specific for (4-hydoxy-3-nitrophenyl)acetyl (NP). We have reported that during a T-dependent antibody (Ab) response for a low-affinity NP analog p-nitrophenylacetyl (pNP), although V(H)T/lambda1 and V(H)T/lambda2 IgM were equally produced, V(H)T/lambda2 IgG almost exclusively underwent affinity maturation toward pNP. The initial affinity of V(H)T/lambda2 B cells for pNP was approximately 50-100-fold higher than that of V(H)T/lambda1 B cells, suggesting a role of BCR affinity in recruiting B cells to affinity maturation processes. Here, we investigated whether the intensity of BCR signals could contribute to the selection of V(H)T/lambda2 B cells for affinity maturation. V(H)T/lambda2 B cells were more responsive to pNP than V(H)T/lambda1 B cells in vitro. When CFSE-labeled QM B cells were transferred into the wild type mice where T cells had been primed with chicken gamma-globulin (CGG), QM B cells challenged by pNP-conjugated CGG could be observed to get activated and migrate to GCs in the early phase of the T-dependent response to pNP-CGG. Adoptive transfer of sorted populations revealed that the V(H)T/lambda2 B cell population was more potent in migration into GCs than the V(H)T/lambda1 counterpart. Thus, it is suggested that the higher BCR affinity of V(H)T/lambda2 B cells may be an initial cue for their recruitment to GCs during a T-dependent Ab response.
Kouyama
Emi
E
Department of Bioscience and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-Naka, Okayama 700-8530, Japan.
Nishikawa
Yumiko
Y
Okazawa
Takahiro
T
Magari
Masaki
M
Ohmori
Hitoshi
H
Kanayama
Naoki
N
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009596:Nitrophenols / Q000737:chemistry / Q000276:immunology; D010648:Phenylacetates; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D007143:Immunoglobulin Heavy Chains; D009596:Nitrophenols; D010648:Phenylacetates; D011947:Receptors, Antigen, B-Cell; C026242:4-hydroxy-5-nitrophenyl acetic acid