Impaired germinal center responses and suppression of local IgG production during intracellular bacterial infection.
Germinal centers (GCs) are specialized microenvironments in secondary lymphoid organs that facilitate the development of high-affinity, isotype-switched Abs, and immunological memory; consequently, many infections require GC-derived IgG for pathogen clearance. Although Ehrlichia muris infection elicits a robust expansion of splenic, IgM-secreting plasmablasts, we detected only very low frequencies of isotype-switched IgG-secreting cells in mouse spleens, until at least 3 wk postinfection. Instead, Ag-specific IgG was produced in lymph nodes, where it required CD4 T cell help. Consistent with these findings, organized GCs and phenotypically defined splenic GC B cells were found in lymph nodes, but not spleens. Ehrlichial infection also inhibited spleen IgG responses against a coadministered T cell-dependent Ag, hapten 4-hydroxy-3-nitrophenyl acetyl (NP)-conjugated chicken gamma globulin in alum. NP-specific B cells failed to undergo expansion and differentiation into GC B cells in the spleen, Ab titers were reduced, and splenic IgG production was inhibited nearly 10-fold when the Ag was administered during infection. Our data provide a mechanism whereby an intracellular bacterial infection can compromise local immunity to coinfecting pathogens or antigenic challenge.
Racine
Rachael
R
Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, NY 12201, USA.
Jones
Derek D
DD
Chatterjee
Madhumouli
M
McLaughlin
Maura
M
Macnamara
Katherine C
KC
Winslow
Gary M
GM
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004536:Ehrlichia / Q000276:immunology*; D016873:Ehrlichiosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D018858:Germinal Center / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007165:Immunosuppression Therapy; D007424:Intracellular Fluid / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology / Q000382:microbiology / Q000473:pathology
D000907:Antibodies, Bacterial; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D007075:Immunoglobulin M