Signaling via major histocompatibility complex class II molecules and antigen receptors enhances the B cell response to gp39/CD40 ligand

Gail A. Bishop, Wendy D. Warren, Michael T Berton

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Activated T cells induce proliferation and differentiation of resting 13 cells in vitro through their CD40 molecules and lymphokine receptors. However, despite constitutive B cell expression of CD40 and lymphokine receptors, widespread nonspecific polyclonal B cell activation by activated T cells is seldom observed in vivo. The present study was designed to test the hypothesis that signals delivered via the B cell antigen (Ag) receptor (membrane immunoglobulin, mIg) and major histocompatibility complex (MHC) class II molecules enhance B cell responsiveness to CD40-mediated signals, providing specificity to the Ag-nonspecific, MHC-unrestricted CD40 signal. To test this hypothesis, both an Ag-specific mouse B cell clone CH12.LX, and freshly isolated resting splenic B cells were cultured with either soluble or membrane-bound forms of the T cell ligand for CD40 (CD40L), in the presence or absence of additional signals provided by Ag or anti-IgM, interleukin-4, and class-II-specific monoclonal antibody (mAb). Differentiation of CH12.LX cells and proliferation of splenic B cells in response to both forms of CD40L was greatly enhanced by exposure to mIg-mediated signals, with greatest enhancement seen when cells were cultured with Ag prior to receiving other signals. Response to CD40L was further enhanced by concurrent culture with class-II-specific, but not class I-specific mAb. Enhancement was greatest at limiting concentrations of CD40L. The ability of class II MHC-mediated signals to enhance Ag-specific B cell responsiveness to CD40-mediated signaling may selectively promote the activation of B cell clones capable of cognate interactions with helper T cells.

Original languageEnglish (US)
Pages (from-to)1230-1238
Number of pages9
JournalEuropean Journal of Immunology
Volume25
Issue number5
DOIs
StatePublished - May 1995

Fingerprint

CD40 Ligand
Antigen Receptors
Histocompatibility Antigens Class II
Major Histocompatibility Complex
B-Lymphocytes
Antigens
Lymphokines
T-Lymphocytes
Membranes
Immunoglobulins
Clone Cells
Monoclonal Antibodies
Cell Proliferation
B-Cell Antigen Receptors
Helper-Inducer T-Lymphocytes
Interleukin-4
Cell Differentiation
Cultured Cells

Keywords

  • Activation
  • B lymphocyte
  • CD40
  • Class II
  • Immunoglobulin

ASJC Scopus subject areas

  • Immunology

Cite this

Signaling via major histocompatibility complex class II molecules and antigen receptors enhances the B cell response to gp39/CD40 ligand. / Bishop, Gail A.; Warren, Wendy D.; Berton, Michael T.

In: European Journal of Immunology, Vol. 25, No. 5, 05.1995, p. 1230-1238.

Research output: Contribution to journalArticle

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