Back to Search
Start Over
Molecular characterization of the early B cell response to pulmonary Cryptococcus neoformans infection.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2012 Dec 15; Vol. 189 (12), pp. 5820-30. Date of Electronic Publication: 2012 Nov 21. - Publication Year :
- 2012
-
Abstract
- The role of B cells in host defense against fungi has been difficult to establish. We quantified and determined the molecular derivation of B-1a, B-1b, and B-2 B cell populations in C57BL/6 mice after pulmonary infection with Cryptococcus neoformans. Total B-1 and B-2 cell numbers increased in lungs and peritoneal cavity as early as day 1 postinfection, but lacked signs of clonal expansion. Labeled capsular (24067) and acapsular (Cap67) C. neoformans strains were used to identify C. neoformans-binding B cell subsets by flow cytometry. Peritoneal cavity B-1a B cells exhibited the most acapsular and capsular C. neoformans binding in C. neoformans-infected mice, and C. neoformans-selected B-1 B cells secreted laminarin- and C. neoformans-binding IgM. Single-cell PCR-based sequence analysis of B-1a, B-1b, and B-2 cell IgH V region H chain (V(H)) genes revealed increased usage of V(H)11 and V(H)12, respectively, in acapsular and capsular C. neoformans-selected B-1a cells. Germline V(H) segments were used, with capsular C. neoformans-selected cells having less junctional diversity than acapsular C. neoformans-selected cells. Further studies in B-1 B cell-depleted mice showed that these mice had higher brain and lung fungal burdens and less alveolar macrophage phagocytosis of C. neoformans than did control and B-1a B cell-reconstituted mice. Taken together, these results establish a mechanistic role for B-1 B cells in the innate B cell response to pulmonary infection with C. neoformans and reveal that IgM-producing B-1a cells, which express germline V(H) genes, bind C. neoformans and contribute to early fungal clearance. Thus, B-1a B cells provide a first line of defense during pulmonary C. neoformans infection in mice.
- Subjects :
- Animals
B-Lymphocyte Subsets pathology
Cryptococcosis pathology
Immunoglobulin Heavy Chains biosynthesis
Immunoglobulin Variable Region biosynthesis
Lung Diseases, Fungal pathology
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Peritoneal Cavity microbiology
Peritoneal Cavity pathology
B-Lymphocyte Subsets immunology
B-Lymphocyte Subsets microbiology
Cryptococcosis immunology
Cryptococcosis microbiology
Cryptococcus neoformans immunology
Lung Diseases, Fungal immunology
Lung Diseases, Fungal microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 189
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 23175699
- Full Text :
- https://doi.org/10.4049/jimmunol.1201514