Genetic control of B cell activation by bacterial lipopolysaccharide is mediated by multiple distinct genes or alleles

L. M. Glode, D. L. Rosenstreich

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Eleven closely related C3H mouse strains were examined for differences in their DNA synthetic response to a highly descriminatory endotoxin, LPS Escherichia coli K 235. Strains of the C3H line were found to be either high, intermediate, or low responders to endotoxin. Three stains, C3H/St, C3H/Bi, and C3H/CR were high responders. Six strains, C3H/He, C3HfB/He, C3H/Hen, C3Heb/Fej, C3H/DiSn, and C3H/A(vy) were intermediate responders, suggesting that a mutation producing decreased LPS responsiveness occurred in the C3H/He(C3H/An) strain between 1931 and 1945. Two strains, C3H/HeJ and C3H/Bts were unresponsive due to a mutation that occurred between 1960 and 1968. Breeding experiments among high, intermediate, and low responding strains documented probable codominant genetic control by the genes or alleles in the C3H/HeN and C3H/HeJ strains. In the C3H/HeN x C3H/St cross, dominance of the C3H/St gene over the C3H/He gene was documented, whereas the C3H/HeJ x C3H/St cross indicated codominance of these two genes. These findings may represent either three alleles or three distinct genes in C3H mice. A second X linked gene locus was documented in the CBA/N strain which also causes impaired B cell responsiveness to LPS E. coli K235 in serum free conditions. The abnormal gene products in the CBA/N AND C3H/HeJ strains exhibit complementarity since F1 female animals from the cross between two unresponsive strains are responsive to LPS. We conclude that there is at least one distinct X linked gene locus and either three additional autosomal genes or three possible alleles at one or more autosomal loci which determine the LPS sensitivity of murine B cells.

Original languageEnglish (US)
Pages (from-to)2061-2066
Number of pages6
JournalJournal of Immunology
Volume117
Issue number6
StatePublished - Dec 1 1976
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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