B-cell abnormalities in AIDS: stable and clonally-restricted antibody response in HIV-1 infection.
Antibodies in sera of HIV-1 infected individuals against the HIV-1 core protein (p24), HIV-1 envelope glycoprotein (gp120) and reverse transcriptase (RT) are characterized by a skewed light chain isotype expression. The kappa/lambda ratios of antibodies to p24 and gp120 in infected individuals were found to be unique in each individual, but constant over several years independently from disease progression. The oligoclonal nature of the anti-HIV-1 antibodies suggested by skewed kappa/lambda expression was confirmed with isoelectric focusing of affinity purified antibodies to p24 and gp120. Analysis of the utilization of V gene families in purified anti-p24 and anti-gp120 antibodies revealed a restricted and biased VH gene family usage. In contrast, the utilization of VK gene families appeared to be random. The finding of stable and restricted antibody responses in infected individuals could be one of the causes for the failure to produce antibodies to HIV-1 that are effective against escape virus variants.
Müller
S
S
L.P. Markey Cancer Center, University of Kentucky, Lexington 40536.
Wang
H
H
Silverman
G J
GJ
Bramlet
G
G
Haigwood
N
N
Köhler
H
H
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005803:Genes, Immunoglobulin / Q000276:immunology; D015483:HIV Antibodies / Q000032:analysis*; D016655:HIV Core Protein p24 / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007145:Immunoglobulin kappa-Chains / Q000032:analysis; D007146:Immunoglobulin lambda-Chains / Q000032:analysis; D007525:Isoelectric Focusing; D012194:RNA-Directed DNA Polymerase / Q000276:immunology
D015483:HIV Antibodies; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D007132:Immunoglobulin Isotypes; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase