B lymphocytes are not required for murine resistance to the human filarial parasite, Brugia malayi. 1995

T V Rajan, and L D Shultz, and J Yates, and D L Greiner
Department of Pathology, University of Connecticut Health Center, Farmington 06030, USA.

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.

UI MeSH Term Description Entries
D007136 Immunoglobulins Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses. Globulins, Immune,Immune Globulin,Immune Globulins,Immunoglobulin,Globulin, Immune
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008817 Mice, Mutant Strains Mice bearing mutant genes which are phenotypically expressed in the animals. Mouse, Mutant Strain,Mutant Mouse Strain,Mutant Strain of Mouse,Mutant Strains of Mice,Mice Mutant Strain,Mice Mutant Strains,Mouse Mutant Strain,Mouse Mutant Strains,Mouse Strain, Mutant,Mouse Strains, Mutant,Mutant Mouse Strains,Mutant Strain Mouse,Mutant Strains Mice,Strain Mouse, Mutant,Strain, Mutant Mouse,Strains Mice, Mutant,Strains, Mutant Mouse
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D005368 Filariasis Infections with nematodes of the superfamily FILARIOIDEA. The presence of living worms in the body is mainly asymptomatic but the death of adult worms leads to granulomatous inflammation and permanent fibrosis. Organisms of the genus Elaeophora infect wild elk and domestic sheep causing ischemic necrosis of the brain, blindness, and dermatosis of the face. Elaeophoriasis,Filarioidea Infections,Infections, Filarioidea,Elaeophoriases,Filariases,Filarioidea Infection,Infection, Filarioidea
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000909 Antibodies, Helminth Immunoglobulins produced in a response to HELMINTH ANTIGENS. Helminth Antibodies
D001402 B-Lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D013154 Spleen An encapsulated lymphatic organ through which venous blood filters.

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