Foy T M, Laman J D, Ledbetter J A, Aruffo A, Claassen E, Noelle R J
Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756.
J Exp Med. 1994 Jul 1;180(1):157-63. doi: 10.1084/jem.180.1.157.
gp39, the ligand for CD40 expressed on activated CD4+ T helper cells, is required for the generation of antibody responses to T-dependent (TD) antigens. Treatment of mice with anti-gp39 in vivo inhibits both primary and secondary antibody formation to TD, but not T-independent antigens. However, the role of this receptor-ligand pair in the development of germinal centers and the generation of B cell memory is as yet undefined. Using an antibody to gp39, this study examines the in vivo requirement for gp39-CD40 interactions in the induction of germinal center formation, as well as in the generation of B cell memory. Animals were immunized, treated in vivo with anti-gp39, and evaluated using immunohistochemical staining for the presence of splenic germinal centers 9-11 d after immunization. The results demonstrate that the formation of germinal centers was completely inhibited as a result of treatment with anti-gp39. Moreover, adoptive transfer experiments demonstrate that the generation of antigen-specific memory B cells is also inhibited as a consequence of blocking gp39-CD40 interactions. Taken together, the data demonstrate that gp39-CD40 interactions are critical not only for the generation of antibody responses, but also in the development of B cell memory.
gp39是活化的CD4 + T辅助细胞上表达的CD40配体，是产生针对T依赖性（TD）抗原的抗体反应所必需的。在体内用抗gp39治疗小鼠会抑制对TD的初次和二次抗体形成，但不影响对非T依赖性抗原的抗体形成。然而，这种受体-配体对在生发中心发育和B细胞记忆产生中的作用尚未明确。本研究使用抗gp39抗体，研究了体内gp39-CD40相互作用在诱导生发中心形成以及产生B细胞记忆中的必要性。对动物进行免疫，在体内用抗gp39治疗，并在免疫后9 - 11天使用免疫组织化学染色评估脾脏生发中心的存在情况。结果表明，抗gp39治疗可完全抑制生发中心的形成。此外，过继转移实验表明，阻断gp39-CD40相互作用也会抑制抗原特异性记忆B细胞的产生。综上所述，数据表明gp39-CD40相互作用不仅对抗体反应的产生至关重要，而且对B细胞记忆的发育也至关重要。
