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CD134L Engagement Enhances Human B Cell Ig Production: CD154/CD40, CD70/CD27, and CD134/CD134L Interactions Coordinately Regulate T Cell-Dependent B Cell Responses¹

Shinji Morimoto^*,,, Yumiko Kanno^*, Yuetsu Tanaka^§, Yoshiaki Tokano, Hiroshi Hashimoto, Serge Jacquot^||, Chikao Morimoto^||, Stuart F. Schlossman^||, Hideo Yagita^,¶, Ko Okumura^,¶ and Tetsuji Kobata^2,*,

^* Division of Immunology, Institute for Medical Science, Dokkyo University School of Medicine, Tochigi, Japan; Departments of Immunology and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan; ^§ Department of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Science, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan; ^¶ Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, Tokyo, Japan; and ^|| Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115

CD134 is a member of the TNFR family expressed on activated T cells, whose ligand, CD134L, is found preferentially on activated B cells. We have previously reported that the CD70/CD27 interaction may be more important in the induction of plasma cell differentiation after the expansion phase induced by the CD154/CD40 interaction has occurred. When CD134-transfected cells were added to PBMCs stimulated with pokeweed mitogen, IgG production was enhanced in a dose-dependent fashion. Addition of CD134-transfected cells to B cells stimulated with Staphylococcus aureus Cowan I strain/IL-2 resulted in little if any enhancement of B cell IgG production and proliferation. We found that while CD134-transfected cells induced no IgG production by themselves, it greatly enhanced IgG production in the presence of CD40 stimulation or T cell cytokines such as IL-4 and IL-10. The addition of CD134-transfected cells showed only a slight increase in the number of plasma cells compared with that in the culture without them, indicating that an increased Ig production rate per cell is responsible for the observed enhancing effect of CD134L engagement rather than increase in plasma cell generation. These results strongly suggest different and sequential roles of the TNF/TNFR family molecules in human T cell-dependent B cell responses through cell-cell contacts and the cytokine network.