Nef protein of HIV-1 has B-cell stimulatory activity

Narendra Chirmule, Naoki Oyaizu, Carl Saxinger, Savita Pahwa

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Objective: To examine the B-cell stimulatory properties of the regulatory Nef protein of HIV-1. Methods: The effect of the HIV-1 regulatory proteins Nef, Tat and Vif, were analyzed for their ability to induce differentiation of normal B lymphocytes into immunoglobulin secreting cells (ISC). Results: A recombinant Nef protein, but neither Tat or Vif, was able to induce ISC in peripheral blood lymphocyte (PBL) cultures of HIV-1-seronegative donors. Another recombinant Nef protein, d-Nef, with a truncated amino terminal (deletion of 34 amino acids) failed to induce B-cell differentiation. Pretreatment of the Nef protein with a polyclonal anti-Nef-antibody abrogated its B-cell stimulatory activity. The Nef-induced B-cell differentiation was dependent on cell-to-cell contact. Cell surface molecules leukocyte function-associated molecule (LFA)-1, intracellular adhesion molecule (ICAM)-1, human lymphocyte antigen-DR and B7 were involved in the T-B-cell interaction because monoclonal antibodies to these molecules abrogated the Nef-induced B-cell differentiation response. The Nef protein was able to induce interleukin (IL)-6 messenger (m)RNA and IL-6 protein secretion in PBL, with monocytes as the primary source. Conclusions: These findings indicate that regulatory (Nef) proteins of HIV-1 contribute to the intense B-cell activation that occurs in association with HIV-1 infection. T-B-cell contact-dependent interaction and induction of IL-6 by these proteins appear to play major roles in this process.

Original languageEnglish (US)
Pages (from-to)733-739
Number of pages7
Issue number6
StatePublished - Jun 1994
Externally publishedYes


  • B-cell differentiation
  • Interleukin-6
  • Nef
  • T-B-cell contact

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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