title: Novel role of the Ras cascade in memory B cell response.
abstract: Engagement of the B cell antigen receptor (BCR) triggers the Ras cascade, but the biological role of the latter in B cell response is unknown. Here, we report that in T cell-dependent response, the role of the Ras cascade is confined to memory B cells and possibly marginal zone B cells. When Ras-dependent BCR signaling was impaired, the generation of IgG germinal center B cells was unaffected but the recruitment of high-affinity cells into the memory compartment and terminal differentiation were inhibited. Furthermore, inhibition of MEK activity consistently impaired antibody production by IgG memory B cells (but not naïve B cells) in vitro. Notably, this impairment was countered by overexpression of Bcl-2. Thus, our data suggest that upon antigen stimulation, memory B cells are susceptible to apoptosis but can be rescued via an antiapoptotic effect mediated through the Ras cascade.
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Ayako
authors.initials: A
authors.lastname: Inamine
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Sachiko
authors.initials: S
authors.lastname: Haraguchi
authors.forename: Emi
authors.initials: E
authors.lastname: Yoshioka
authors.forename: Naoya
authors.initials: N
authors.lastname: Kojima
authors.forename: Ryo
authors.initials: R
authors.lastname: Abe
authors.forename: Toshitada
authors.initials: T
authors.lastname: Takemori
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D000941:Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D018631:ras Proteins