Title

B1 B lymphocytes play a critical role in host protection against lymphatic filarial parasites.

Document Type

Article

Publication Date

2000

Keywords

B-Lymphocyte-Subsets, B-Lymphocytes, Brugia-malayi, Brugia-pahangi, Filariasis, Flow-Cytometry, Immunocompetence, Mice, Mice-Inbred-C57BL, Mice-Inbred-DBA, Mice-SCID, Species-Specificity, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes

JAX Source

J Exp Med 2000 Feb; 191(4):731-735.

Grant

AI39705/AI/NIAID, AI42362/AI/NIAID, AI30389/AI/NIAID

Abstract

Host defense against multicellular, extracellular pathogens such as nematode parasites is believed to be mediated largely, if not exclusively, by T lymphocytes. During our investigations into the course of Brugia malayi and Brugia pahangi infections in immunodeficient mouse models, we found that mice lacking B lymphocytes were permissive for Brugian infections, whereas immunocompetent mice were uniformly resistant. Mice bearing the Btk(xid) mutation were as permissive as those lacking all B cells, suggesting that the B1 subset may be responsible for host protection. Reconstitution of immunodeficient recombination activating gene (Rag)-1(-/)- mice with B1 B cells conferred resistance, even in the absence of conventional B2 lymphocytes and most T cells. These results suggest that B1 B cells are necessary to mediate host resistance to Brugian infection. Our data are consistent with a model wherein early resistance to B. malayi is mediated by humoral immune response, with a significant attrition of the incoming infectious larval load. Sterile clearance of the remaining parasite burden appears to require cell-mediated immunity. These data raise the possibility that the identification of molecule(s) recognized by humoral immune mechanisms might help generate prophylactic vaccines.