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 journalArticle

173 Citations (Scopus)

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 - 1995

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CD40 Ligand
B-Lymphocytes
Cell Line
Hybridomas
T-Lymphocytes
Calcium Ionophores
Membrane Glycoproteins
Phorbol Esters

ASJC Scopus subject areas

  • Immunology

Cite this

Grammer, A. C., Bergman, M. C., Miura, Y., Fujita, K., Davis, L. S., & Lipsky, P. E. (1995). The CD40 ligand expressed by human B cells costimulates B cell responses. Journal of Immunology, 154(10), 4996-5010.

The CD40 ligand expressed by human B cells costimulates B cell responses. / Grammer, A. C.; Bergman, M. C.; Miura, Y.; Fujita, K.; Davis, L. S.; Lipsky, P. E.

In: Journal of Immunology, Vol. 154, No. 10, 1995, p. 4996-5010.

Research output: Contribution to journalArticle

Grammer, AC, Bergman, MC, Miura, Y, Fujita, K, Davis, LS & Lipsky, PE 1995, 'The CD40 ligand expressed by human B cells costimulates B cell responses', Journal of Immunology, vol. 154, no. 10, pp. 4996-5010.
Grammer AC, Bergman MC, Miura Y, Fujita K, Davis LS, Lipsky PE. The CD40 ligand expressed by human B cells costimulates B cell responses. Journal of Immunology. 1995;154(10):4996-5010.
Grammer, A. C. ; Bergman, M. C. ; Miura, Y. ; Fujita, K. ; Davis, L. S. ; Lipsky, P. E. / The CD40 ligand expressed by human B cells costimulates B cell responses. In: Journal of Immunology. 1995 ; Vol. 154, No. 10. pp. 4996-5010.
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