title: HIV-gp 160-induced T cell-dependent B cell differentiation. Role of T cell-B cell activation molecule and IL-6.
abstract: The HIV envelope glycoprotein gp160 has been previously demonstrated to induce differentiation of normal B lymphocytes into Ig-secreting cells; the response is T cell-dependent, and T cells pretreated with gp160 can support B cell differentiation. This study investigates the cell surface molecules and cytokines that play a role in the gp160-induced T-B cell interaction. Utilizing CD4+CD45RO+ cloned T cells as the source of helper cells, we observed that physical contact with B cells is essential for the gp160-induced B cell response; no IgG-secretion occurred if T cells were separated from the B cells by culturing them in Transwell chambers. The expression of T cell-B cell activation molecule, a novel surface molecule associated with T cell activation, was moderately increased by gp160, and antibody to T cell-B cell activation molecule abrogated the gp160-mediated Th cell function. Cell surface molecules LFA-1, ICAM-1, HLA-DR, CD28, and B7 were also involved in the T-B cell interaction since mAb to any of these molecules inhibited the gp160-induced B cell differentiation response. gp160 also induced IL-6R and CD23 molecule expression on B cells when added to cultures of T plus B cells; there was CD23 expression only in cells that formed conjugates with T cells. Paraforamaldehyde-fixed, gp160-pretreated T cells failed to elicit IgG responses in B cells, but did induce CD23 and IL-6R up-regulation on B cells. Addition of exogenous IL-6, but not IL-2 or IL-4, restored the IgG secretion. These findings indicate that the T cell dependence for gp160-induced B cell differentiation responses involves two steps: one requires contact-dependent interaction of several cell surface molecules, and the second requires IL-6 secretion.
authors.affiliation: Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030.
authors.forename: N
authors.initials: N
authors.lastname: Chirmule
authors.forename: V S
authors.initials: VS
authors.lastname: Kalyanaraman
authors.forename: S
authors.initials: S
authors.lastname: Lederman
authors.forename: N
authors.initials: N
authors.lastname: Oyaizu
authors.forename: H
authors.initials: H
authors.lastname: Yagura
authors.forename: M J
authors.initials: MJ
authors.lastname: Yellin
authors.forename: L
authors.initials: L
authors.lastname: Chess
authors.forename: S
authors.initials: S
authors.lastname: Pahwa
mesh_terms: D000944:Antigens, Differentiation, B-Lymphocyte / Q000187:drug effects / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000187:drug effects / Q000502:physiology*; D015704:CD4 Antigens; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects; D005404:Fixatives; D005557:Formaldehyde; D015686:Gene Products, env / Q000494:pharmacology*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008211:Lymphocyte Cooperation / Q000187:drug effects; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D011108:Polymers; D011498:Protein Precursors / Q000494:pharmacology*; D017455:Receptors, IgE / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D005404:Fixatives; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D015850:Interleukin-6; D011108:Polymers; D011498:Protein Precursors; D017455:Receptors, IgE; D005557:Formaldehyde; C003043:paraform