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Biomedical subjects

W Humphrey

Publications and source records attributed to W Humphrey.

24 records · Page 2Linked to original sources

Idiotype of inulin-binding antibodies and myeloma proteins controlled by genes linked to the allotype locus of the mouse.

The serum from non-immunized mice of strains BALB/c, C58, A/He, and RIII contained hemagglutinins for stearoyl inulin-coated SRBC. Immunization with bacterial levan slightly elevated these titers. These same sera also carried cross-specific idiotypic determinants (IdX) that are associated only with inulin-binding myeloma proteins (INBMP) of BLAB/c mice. Three InuldX specificities, A, B, and G, were identified. The InuIdX phenotypes of strains BALB/c, C58, and A/He were InuIdXA+B+G+; strain RIII was InuIdX A+B-G+; strain C57BL/6, C57BL/10, DBA/2, AKR and NH were A-B-G-. Strains CBA, C3H, PL, and C57L could not be typed because of low and inconsistent levels of InuIdX and anti-inulin hemagglutinins. The InuIdXA+B+G+ phenotype was used as a genetic marker in immunoglobulin congenic strains CB-20, BAB-14, and BC-8 and in Bailey RI strains which are derived from crosses of BALB/c (InuIdXA+B+G+) and C57BL/ka or C57BL/6, respectively (InuldXA-B-G-). Linkage of the IdXA+B+G+ to the BALB/c a allotype locus was demonstrated. In addition, the InuldXA+B+G+ marker was used as a phenotype in an analysis of 168 first generation backcorss progeny (C57BL X (C57BL X BALB/c) F). Linkage of the marker to the BALB/c allotype was found again. Two proven recombinant mice having the C57BL a allotype and the InuIdxA+B+G+ markers were identified and progeny tested. Four other potential crossover types are still being progeny-tested.

Animals↗

Multiple individual and cross-specific indiotypes on 13 levan-binding myeloma proteins of BALB/c mice.

13 leven-binding myeloma proteins (LBMP) of BALB/c origin were classified into two groups with different binding specificities; one group of 11 proteins bound beta2 leads to 1 fructosans, a second group of two proteins bound fructosans probably of beta2 leads to 6 linkage. Anti-idiotypic sera prepared to 10 of the proteins in the appropriate strains of mice identified numerous idiotypic determinants. Each protein used for immunization had its own unique individual idiotypic specificities (IdI) and in addition most of the proteins carried two-nine cross-specific or shared idiotypes (IdX) that were found only among LBMP, and not found in 106 non-LBMP. Most of the IdX determinants and only four of the IdI determinants of the beta2 leads to 1 fructosan binding group were located in the antigen-binding site. The multiplicity of antigenic differences in this functionally related group of immunoglobulins reveals an unexpected degree of heterogeneity in V-regions that appears to be unrelated to binding.

Animals↗

Genetics of a new IgVH (T15 idiotype) marker in the mouse regulating natural antibody to phosphorylcholine.

The idiotype present on the Fab of a phosphorylcholine-binding IgA myeloma protein TEPC 15 (T15) of BALB/c origin was found in normal serum of BALB/c mice. Molecules carrying the T15 idiotype in normal serum could be adsorbed with Sepharose phosphorylcholine beads and R36A pneumococci. The T15 idiotype is absent in germ-free BALB/c but appears when the mice are conventionalized. A survey of normal sera of inbred strains for the T15 idiotype showed it to be present in BALB/c, 129, C57L, C58, and ST and absent or in low levels in CBA, C3H, C57BL/6, C57BL/Ka, C57BL/10, SJL, B10.D2, DBA/2, RIII, A, AL, AKR, NZB, and NH inbred strains of mice. The T15 idiotype is associated with some but not all strains carrying the IgC(H) allotypes found in BALB/c. Linkage of genes controlling the T15 idiotype in normal serum to the IgC(H) locus of BALB/c was demonstrated in F(2) progeny of a BALB/c and C57BL cross, Bailey's recombinant inbred strains, C x BD, C x BE, C x BG, C x BH, C x BI, C x BJ, C x BK, and CB20 congenic strains. Among these strains, only those possessing the IgC(H) locus of BALB/c including the F(2) progeny consisting of BALB/c homozygotes and BALB/c/C57BL heterozygotes and C x BG and C x BJ recombinants showed the T15 idiotype.

Animals↗

Association of H-2 types with genetic control of immune reponsiveness to IgG (gamma2a) allotypes in the mouse.

Immune responsiveness to IgG allotypes in the mouse was found to be controlled by an immune response gene Ir-IgG linked to the H-2 locus. This was demonstrated by the analysis of the immune response to BALB/c IgG (gamma2a) myeloma proteins in mice of various H-2 types from five different linkage groups of immunoglobulin heavy chains. Antisera were examined for antibodies to idiotypic (Fab) and allotypic (Fc) specificities. No immune response to BALB/c IgG myeloma proteins was found in mice with the same heavy-chain immunoglobulin linkage group as BALB/c but of different H-2 types. In mice with immunoglobulin heavy chains that are different than BALB/c, a high immune response to IgG myeloma proteins was found in H-2 types b, bc, p, r, s, and v; a low response in a, d, k, and q. The Ir-IgG gene is controlled by a dominant autosomal gene.

Animals↗

H-2-linked immune response (Ir) genes. Independent loci for Ir-IgG and Ir-IgA genes.

Two H-2-linked autosomal dominant immune response (Ir) genes Ir-IgG and Ir-IgA were demonstrated to be at separate loci. Ir-IgG controls the immune response to IgG (gamma2a) myeloma proteins and Ir-IgA the immune response to IgA meyloma proteins. Both genes are associated with the H-2K region specificities of the H-2 chromosome, specifically Ir-IgG with H-2(b) and Ir-IgA with H-2(a). Different recombinants derived from H-2(a)/H-2(b) crossovers were examined for their immune responsiveness to BALB/c IgG (gamma2a) and IgA myeloma proteins. B10 (H-2(b)) parental type responded only to IgG; B10.A (H-2(a)) responded only to IgA. All the recombinants except for B10.A (4R) responded to either IgG or IgA. B10.A (4R), however, responded to both IgG and IgA. This indicated that the crossover event giving rise to B10.A (4R) occurred between the Ir-IgG and Ir-IgA loci.

Animals↗

Association of H-2 types with genetic control of immune responsiveness to IgA allotypes in the mouse.

The immune response to BALB/c IgA myeloma proteins (Ir-IgA) was determined in mice of various H-2 types from five different linkage groups of immunoglobulin heavy chains (IgC(H)). Antisera were examined for antibodies to idiotypic (Fab) and allotypic (Fc) specificities. No immune response to IgA myeloma proteins was found in mice with the same linkage group as BALB/c but with different H-2 alleles. In mice with immunoglobulin heavy chains that are different than BALB/c, a high immune response to IgA myeloma proteins was found in H-2 types a, k, r, and s; a low response is associated with H-2(b) and H-2(d) types. Chromosome mapping of Ir-IgA genes in the H-2 locus indicate that they are on the right side of the chromosome, to the right of the Ss locus. Ir-IgA genes are controlled by dominant autosomal genes.

Animals↗