The CD40 ligand expressed by human B cells costimulates B cell responses

A. C. Grammer, M. C. Bergman, Y. Miura, K. Fujita, L. S. Davis, P. E. Lipsky

Research output: Contribution to journalArticlepeer-review

175 Scopus citations

Abstract

The possibility that activated B cells might express a ligand for CD40 that was of functional importance for B cell responses was examined by using highly purified human peripheral blood B cells, as well as a variety of B lymphoblastoid cell lines and hybridomas. Following stimulation with the combination of a calcium ionophore and a phorbol ester, human B cells bound a soluble fusion protein containing the extracellular portion of CD40 and the Fc region of lgG1 (CD40.lg). A variety of B cell lines and hybridomas also bound CD40.1g, either constitutively or after activation. In addition, CD40.Ig specifically immunoprecipitated a 33-kDa glycoprotein from surface 125I-labeled activated B cells. The nucleotide sequence of the coding region of the CD40 ligand mRNA amplified by RT-PCR from activated T cells and B cell lines was identical. The CD40 ligand expressed on human B cells was important functionally because homotypic aggregation of CD40 ligand- expressing B cells was inhibited by the CD40.Ig construct. Additionally, RNA and DNA synthesis as well as Ig production by polyclonally activated, highly purified peripheral B cells and a variety of B cell lines were inhibited significantly by the CD40.Ig construct. Finally, B cell lines expressing the CD40 ligand induced Ig production from resting normal B cells in a CD40- dependent manner. These results indicate that human B cell is express a ligand for CD40 that is identical with that expressed by activated T cells and that the B cell-expressed CD40 ligand plays an important role in facilitating responses of activated B cells.

Original languageEnglish (US)
Pages (from-to)4996-5010
Number of pages15
JournalJournal of Immunology
Volume154
Issue number10
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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