Mucosal plasma cell repertoire during HIV-1 infection.
Impaired development of local Ab responses may predispose HIV-1-infected patients to an increased rate, severity, and duration of mucosal infections. We characterized the repertoire of Ig-producing cells in the intestinal effector compartment (the lamina propria) of HIV-1-infected (n = 29) and seronegative control (n = 27) subjects. The density of Ig-producing cells per area was similar in both groups. However, the proportions of IgA-producing cells were lower in both the duodenum and colon from HIV-1-infected patients compared with those of control subjects (p < 0.05), with compensatory increases in IgG-producing cells in the colon and IgM-producing cells in the duodenum. Similarly, among Abs in the lumen the proportions of IgA were also decreased and the proportions of IgG were increased among HIV-1-infected patients. On a molecular level, V(H) gene repertoire analyses by RT-PCR revealed comparable proportions of the V(H)3 family among duodenal IgA transcripts (50-53%) from both groups. V(H)3 expression was decreased only for IgM among patients with advanced HIV-1 disease (n = 6) compared with that of control subjects (n = 8) (48 +/- 8 vs 62 +/- 13%; p < 0.01). Moreover, the frequencies of individual IgM and IgA V(H)3 genes were comparable in each group, including rates of putative HIV-1 gp120-binding V(H)3 genes (V3-23, V3-30, V3-30/3-30.5). We conclude that, despite a decrement in local IgA producing cells, the density and molecular V(H) repertoire of mucosal plasma cells are relatively intact among patients with HIV-1 infection. These data suggest that HIV-1-infected patients use functional regulatory mechanisms to provide sufficient V(H) diversity and effective induction and differentiation of mucosal B cells.
Scamurra
Ronald W
RW
Mucosal and Vaccine Research Center, Veteran Affairs Medical Center, University of Minnesota School of Medicine, Minneapolis, MN 55417, USA.
Nelson
Douglas B
DB
Lin
Xue Mei
XM
Miller
Darren J
DJ
Silverman
Gregg J
GJ
Kappel
Tim
T
Thurn
Joseph R
JR
Lorenz
Erin
E
Kulkarni-Narla
Anjali
A
Janoff
Edward N
EN
D000328:Adult; D003106:Colon / Q000473:pathology; D004386:Duodenum / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005787:Gene Frequency / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D007413:Intestinal Mucosa / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D005810:Multigene Family / Q000276:immunology; D010950:Plasma Cells / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007507:Therapeutic Irrigation
D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region