Antibody repertoire against HIV-1 gp120 triggered in nude and normal mice by GM-CSF/gp120 immunization.
Granulocyte-macrophage colony stimulating factor (GM-CSF) facilitates the induction of primary immune responses by activating and recruiting antigen-presenting cells (APC), which efficiently present antigen determinants to Th cells. We have derived a functional GM-CSF/gp120 chimeric protein that, following immunization in soluble, adjuvant-independent form in normal mice, triggers highly specific, high affinity anti-gp120 antibodies. In contrast, nude mice respond with mutated, polyreactive, low affinity antibodies that mature further and increase in affinity in T cell-reconstituted nude mice. Anti-gp120 antibody production in nude mice is mediated principally by GM-CSF/gp120-triggered IL-4 production, since neutralizing anti-IL-4 abrogates the in vivo response. The anti-gp120 antibody response in normal, nude and T cell-reconstituted nude mice is encoded at a remarkably high frequency by the VH81X and VH7183 genes, a family used notably during fetal life and, when expressed at the adult stage, associated with autoimmune disease. We conclude that HIV gp120 binds and selects a subpopulation of developing B cells expressing a set of VH genes associated with immunodeficiency and autoimmunity.
del Real
G
G
Department of Immunology and Oncology, Centro Nacional de Biotecnología, UAM, Cantoblanco, Madrid, Spain.
Llorente
M
M
Lucas
P
P
Kremer
L
L
Torán
J L
JL
Martínez-A
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000915:Antibody Affinity; D000918:Antibody Specificity; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001483:Base Sequence; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009154:Mutation; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor