TY - JOUR
T1 - Mucosal plasma cell repertoire during HIV-1 infection
AU - Scamurra, Ronald W.
AU - Nelson, Douglas B.
AU - Lin, Xue Mei
AU - Miller, Darren J.
AU - Silverman, Gregg J.
AU - Kappel, Tim
AU - Thurn, Joseph R.
AU - Lorenz, Erin
AU - Kulkarni-Narla, Anjali
AU - Janoff, Edward N.
PY - 2002/10/1
Y1 - 2002/10/1
N2 - 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, VH gene repertoire analyses by RT-PCR revealed comparable proportions of the VH3 family among duodenal IgA transcripts (50-53%) from both groups. VH3 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 VH3 genes were comparable in each group, including rates of putative HIV-1 gp120-binding VH3 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 VH 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 VH diversity and effective induction and differentiation of mucosal B cells.
AB - 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, VH gene repertoire analyses by RT-PCR revealed comparable proportions of the VH3 family among duodenal IgA transcripts (50-53%) from both groups. VH3 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 VH3 genes were comparable in each group, including rates of putative HIV-1 gp120-binding VH3 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 VH 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 VH diversity and effective induction and differentiation of mucosal B cells.
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U2 - 10.4049/jimmunol.169.7.4008
DO - 10.4049/jimmunol.169.7.4008
M3 - Article
C2 - 12244203
AN - SCOPUS:0036784646
SN - 0022-1767
VL - 169
SP - 4008
EP - 4016
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -