SDF-1α Regulates HIV-1-gp120-Induced Changes in CD79b Surface Expression and Ig Production in Activated Human B Cells

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2002-11, Vol.105 (2), p.208-214
• Main Authors: Nance, Christina L., Shearer, William T.
• Format: Article
• Language: English
• Subjects: B cells; BCR; Biological and medical sciences; CD79b; CXCR4; gp120; Human viral diseases; Infectious diseases; Medical sciences; SDF-1α; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1006/clim.2002.5284

Binding of HIV-1 glycoprotein (gp120) to activated B cells of HIV-infected and HIV-uninfected subjects induces increased cell proliferation, cAMP generation, immunoglobulin (Ig) production and downregulation of the invariant chain, CD79b, of the B-cell receptor. We present evidence that the stromal cell-derived factor-1α (SDF-1α), itself a B-cell stimulant, reversed gp120-driven downregulation of CD79b in CD40- and IL-4-activated purified HIV-1 seronegative human peripheral blood B cells. SDF-1α augmented gp120-induced Ig production, downregulated CXCR4 receptor expression, and alone, exerted no effect on CD79b surface expression, reversed the gp120-induced downregulation of CD79b. These SDF-1α-modulated B-cell responses were specifically abrogated by an anti-SDF-1α antibody. These data suggest that SDF-1α plays an important regulatory role in the altered B-cell responses seen in HIV-1 infection. Further, these findings may enhance the understanding of the pathophysiology of HIV-1 infection and suggest a strategy utilizing SDF-1α or related molecules as an anti-HIV therapy.