B lymphocytes are not required for murine resistance to the human filarial parasite, Brugia malayi.
Immunocompetent mice are resistant to the growth and development of human lymphatic filarial parasites, including the aperiodic strain of Brugia malayi. We have recently established that mice homozygous for the severe combined immunodeficiency (scid) mutation, and therefore deficient in both T and B lymphocytes, are permissive for infection. This observation suggests that components of the adaptive (antigen-specific) immune system are obligate requirements for murine resistance to B. malayi. In order to determine more precisely the component of the immune system that mediates murine resistance to B. malayi, we have used mouse strains in which individual genes involved in the maturation of specific components of the immune system have been disrupted by homologous recombination. In previous studies, we demonstrated that mice that lack either major histocompatibility (MHC) class I restricted, CD8+ T lymphocytes (beta 2-microglobulin knockout mice; beta 2M-/-) or CD4+ T lymphocytes (CD4 knockout mice; CD4-/-) are as resistant to B. malayi as intact mice. In the current study, we have used mice in which the membrane exon of the immunoglobulin (Ig) mu (heavy chain) constant region gene segment has been disrupted by homologous recombination. These mice cannot develop mature B lymphocytes and lack serum Ig. We demonstrate that such "B-less" mice are completely resistant to B. malayi. These data, taken in combination with the observation that T-cell-deficient athymic mice homozygous for the nu (nude) mutation are fully permissive for infection, suggest that B lymphocytes and their products are neither required nor sufficient to mediate resistance to B. malayi.
Rajan
T V
TV
Department of Pathology, University of Connecticut Health Center, Farmington 06030, USA.
Shultz
L D
LD
Yates
J
J
Greiner
D L
DL
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D017178:Brugia malayi / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005368:Filariasis / Q000276:immunology*; D007136:Immunoglobulins / Q000097:blood; D016130:Immunophenotyping; D016131:Lymphocyte Subsets; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D013154:Spleen / Q000166:cytology
D000909:Antibodies, Helminth; D007136:Immunoglobulins