Cutting edge: HIV-1 Tat protein differentially modulates the B cell response of naive, memory, and germinal center B cells.
Critical steps of B cell differentiation occur within lymphoid organs that are also major sites of HIV-1 replication. Because Tat can be released by infected cells, we investigated whether extracellular HIV-1 Tat modulates cell proliferation of B cells at critical stages of their differentiation. Here we show that extracellular Tat inhibited the proliferation of B cell receptor-triggered naive and memory B cells by >80% but had no effect on their CD40 mAb and IL-4-mediated proliferation. In striking contrast, Tat doubled the germinal center B cell proliferation induced by CD40 mAb and IL-4. These effects were dose dependent and required the addition of Tat at the initiation of the culture, suggesting that Tat acts on early stages of cell cycle progression. By its effects on B cell subsets, Tat might directly affect the normal B cell differentiation process in HIV-positive patients and favor the occurrence of AIDS-associated B cell lymphomas.
Institut National de la Santé et de la Recherche Médicale Unit 131, Institut Paris-sud sur les Cytokines, Clamart, France.
E A
EA
Lefevre
R
R
Krzysiek
E P
EP
Loret
P
P
Galanaud
Y
Y
Richard
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000502:physiology*; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D004306:Dose-Response Relationship, Immunologic; D015696:Gene Products, tat / Q000494:pharmacology / Q000502:physiology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D006131:Growth Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007075:Immunoglobulin M / Q000276:immunology; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007399:Interphase / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D014066:Palatine Tonsil; D054322:tat Gene Products, Human Immunodeficiency Virus
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D015696:Gene Products, tat; D006131:Growth Inhibitors; D007106:Immune Sera; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; C044203:anti-IgM; D054322:tat Gene Products, Human Immunodeficiency Virus; D015847:Interleukin-4