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gp39-CD40 interactions are essential for germinal center formation and the development of B cell memory

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Author: Foy, T.M. · Laman, J.D. · Ledbetter, J.A. · Aruffo, A. · Claassen, E. · Noelle, R.J.
Type:article
Date:1994
Institution: Medisch Biologisch Laboratorium TNO
Source:Journal of Experimental Medicine, 1, 180, 157-163
Identifier: 232636
doi: doi:10.1084/jem.180.1.157
Keywords: cd4 antigen · Ligand · Antibody production · Antibody response · Antigen specificity · Cell maturation · Germinal center · Helper cell · Humoral immunity · Immune response · Immunization · Immunohistochemistry · Memory cell · Mouse · Animal · Antibody Formation · Antigens, CD · Antigens, CD40 · B-Lymphocytes · CD40 Ligand · Immunologic Memory · Membrane Glycoproteins · Mice · Mice, Inbred BALB C

Abstract

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. Chemicals/CAS: Antigens, CD; Antigens, CD40; Antigens, Differentiation, B-Lymphocyte; CD40 Ligand, 147205-72-9; Membrane Glycoproteins