SDF-1alpha regulates HIV-1-gp120-induced changes in CD79b surface expression and Ig production in activated human B cells

• Published in: Clinical immunology (Orlando, Fla.) Vol. 105; no. 2; p. 208
• Main Authors: Nance, Christina L, Shearer, William T
• Format: Journal Article
• Language: English
• Published: United States 01.11.2002
• Subjects: Anti-HIV Agents - pharmacology; Antigens, CD - metabolism; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; CD79 Antigens; Chemokine CXCL12; Chemokines, CXC - pharmacology; Chemokines, CXC - physiology; HIV Envelope Protein gp120 - immunology; HIV Infections - drug therapy; HIV Infections - etiology; HIV Infections - immunology; HIV-1 - immunology; HIV-1 - pathogenicity; Humans; Immunoglobulins - biosynthesis; In Vitro Techniques; Lymphocyte Activation; Receptors, CXCR4 - metabolism; Non-programmatic
• ISSN: 1521-6616
• 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-1alpha (SDF-1alpha), 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-1alpha 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-1alpha-modulated B-cell responses were specifically abrogated by an anti-SDF-1alpha antibody. These data suggest that SDF-1alpha 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-1alpha or related molecules as an anti-HIV therapy.