SDF-1alpha regulates HIV-1-gp120-induced changes in CD79b surface expression and Ig production in activated human B cells.
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.
Nance
Christina L
CL
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA. clnance@texaschildrenshospital.org
Shearer
William T
WT
D019380:Anti-HIV Agents / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D051925:CD79 Antigens; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology* / Q000502:physiology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D019718:Receptors, CXCR4 / Q000378:metabolism
D019380:Anti-HIV Agents; D015703:Antigens, CD; D051925:CD79 Antigens; C497883:CD79B protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015699:HIV Envelope Protein gp120; D007136:Immunoglobulins; D019718:Receptors, CXCR4