Analysis of the role of interferon-gamma, interleukin 2 and a third factor distinct from interferon-gamma and interleukin 2 on human B cell proliferation. Evidence that they act at different times after B cell activation

S. Romagnani, G. M. Giudizi, F. Almerigogna, R. Biagiotti, A. Alessi, C. Mingari, C. M. Liang, L. Moretta, M. Ricci

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Abstract

Recombinant interferon-gamma (rIFN-γ) was able to induce proliferation of human tonsillar B cells activated with suboptimal concentrations of anti-μ antibody. The B cell growth factor (BCGF) activity of rIFN-γ was not due to substances contaminating the IFN-γ preparation, nor was it mediated by factors released by T cells or large granular lymphocytes following activation by rIFN-γ. The response of B cells to rIFN-γ peaked on day 3 of culture and rapidly declined thereafter, whereas the response of parallel anti-μ-activated B cell cultures to recombinant interleukin 2 (rIL 2) appeared on day 3, but continued at least until day 5. In addition, B cells responsive to rIFN-γ could be at least in part separated from those responsive to rIL 2, the former being primarily contained in B cell fractions enriched for high-density small B lymphocytes. Finally, the addition to anti-μ-stimulated B cell cultures of very low concentrations of rIFN-γ potentiated the B cell proliferation promoted by rIL 2. The simultaneous addition of monoclonal antibodies against IFN-γ and T cell activation antigen to anti-μ-stimulated B cell cultures strongly reduced the B cell proliferative response promoted by three different crude BCGF preparations obtained by polyclonal T cell activation in mixed lymphocyte culture. However, the supernatant from a T cell clone (DP5/11) apparently free of IL 2, which manifested a BCGF activity similar to that of rIFN-γ, still maintained its ability to promote proliferation of anti-μ-activated B cells after complete removal of IFN-γ. Taken together, our data indicate that although some T cell clones are able to produce a BCGF distinct from both IFN-γ and IL 2, these lymphokines account for most of the BCGF activity of supernatants obtained from polyclonal T cell populations. They also suggest that IFN-γ and the BCGF distinct from IFN-γ and IL 2 act primarily in the earlier phases of B cell activation and potentiate the proliferative response of activated B cells to IL 2.

Original languageEnglish
Pages (from-to)623-629
Number of pages7
JournalEuropean Journal of Immunology
Volume16
Issue number6
Publication statusPublished - 1986

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Interferon-gamma
Interleukin-2
B-Lymphocytes
Cell Proliferation
Intercellular Signaling Peptides and Proteins
T-Lymphocytes
Cell Culture Techniques
Clone Cells
CD27 Antigens
TCF Transcription Factors
Lymphokines
Lymphocyte Activation

ASJC Scopus subject areas

  • Immunology

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Analysis of the role of interferon-gamma, interleukin 2 and a third factor distinct from interferon-gamma and interleukin 2 on human B cell proliferation. Evidence that they act at different times after B cell activation. / Romagnani, S.; Giudizi, G. M.; Almerigogna, F.; Biagiotti, R.; Alessi, A.; Mingari, C.; Liang, C. M.; Moretta, L.; Ricci, M.

In: European Journal of Immunology, Vol. 16, No. 6, 1986, p. 623-629.

Research output: Contribution to journalArticle

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abstract = "Recombinant interferon-gamma (rIFN-γ) was able to induce proliferation of human tonsillar B cells activated with suboptimal concentrations of anti-μ antibody. The B cell growth factor (BCGF) activity of rIFN-γ was not due to substances contaminating the IFN-γ preparation, nor was it mediated by factors released by T cells or large granular lymphocytes following activation by rIFN-γ. The response of B cells to rIFN-γ peaked on day 3 of culture and rapidly declined thereafter, whereas the response of parallel anti-μ-activated B cell cultures to recombinant interleukin 2 (rIL 2) appeared on day 3, but continued at least until day 5. In addition, B cells responsive to rIFN-γ could be at least in part separated from those responsive to rIL 2, the former being primarily contained in B cell fractions enriched for high-density small B lymphocytes. Finally, the addition to anti-μ-stimulated B cell cultures of very low concentrations of rIFN-γ potentiated the B cell proliferation promoted by rIL 2. The simultaneous addition of monoclonal antibodies against IFN-γ and T cell activation antigen to anti-μ-stimulated B cell cultures strongly reduced the B cell proliferative response promoted by three different crude BCGF preparations obtained by polyclonal T cell activation in mixed lymphocyte culture. However, the supernatant from a T cell clone (DP5/11) apparently free of IL 2, which manifested a BCGF activity similar to that of rIFN-γ, still maintained its ability to promote proliferation of anti-μ-activated B cells after complete removal of IFN-γ. Taken together, our data indicate that although some T cell clones are able to produce a BCGF distinct from both IFN-γ and IL 2, these lymphokines account for most of the BCGF activity of supernatants obtained from polyclonal T cell populations. They also suggest that IFN-γ and the BCGF distinct from IFN-γ and IL 2 act primarily in the earlier phases of B cell activation and potentiate the proliferative response of activated B cells to IL 2.",
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AU - Romagnani, S.

AU - Giudizi, G. M.

AU - Almerigogna, F.

AU - Biagiotti, R.

AU - Alessi, A.

AU - Mingari, C.

AU - Liang, C. M.

AU - Moretta, L.

AU - Ricci, M.

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