EVIDENCE FOR THE LINKAGE OF THE IGCH LOCUS TO A GENE CONTROLLING THE IDIOTYPIC SPECIFICITY OF ANTI-p-AZOPHENYLARSONATE ANTIBODIES IN STRAIN A MICE

Abstract

Rabbit anti-idiots~ic antisera specific for anti-p-azophenylarsonate (antiAr) t antibodies, raised in an individual strain A / J mouse, recognize determinants on anti-Ar antibodies induced in all members of this strain so far tested. These determinants have been found only on anti-At antibodies and not on normal imnmnoglobulins or on other anti-hapten or anti-protein antibodies induced in this strain (1-3). 2 The determinants on A/J anti-Ar antibodies are thus idiotypic and cross-reactive within the strain. In contrast, anti-Ar antibodies induced in most but not all other strains of mice (1, 3; Pawlak and Nisonoff, manuscript in preparation), lack the cross-reactive A/J idiotypic determinant. For this reason the idiotype of A/J anti-Ar antibody is potentially a genetic marker (phenotype).We report here finding the A/J idiotype on anti-Ar antibodies induced in strain AL/N mice; this strain was derived from an outcrossed strain A mouse (4). Strains AL/N and A/J share a number of characteristics, including similar H-2 complex loci (4) and most but not all IgCH allotypic determinants (5, 6), which are localized to the Fc fragment of the molecule. Strain AL/N then probably shares many genes with strain A/J but, according to Staats (4) cannot be considered a true subline of strain A (4).The presence of the cross-reactive idiotypic determinants on anti-Ar antibodies induced in strain AL/N mice is particularly fortuitous because we have recently completed, at the National Institutes of Health, the development of a congenic strain of BALB/c mice,

Clonal Nature of the Immune Response to Phosphorylcholine

“…This association was observed regardless of strain or antibody titer and occurred throughout a primary and secondary response. This contrasts with other systems, including that defined with the mouse antisera in the present work, in which intra-and interstrain variabilities in expression of an idiotype are usual (18)(19)(20)(21)(22)(23). KShler has recent evidence in the in vitro primary anti-PC response which supports the findings presented here.…”

“…5 The fact that the H88 idiotype is present on anti-PC antibodies of all mice, and thus can be considered a species-specific idiotype, clearly distinguishes the immune response to PC from other antibody responses. In systems such as the antistreptococcal and anti-p-azohapten antibody response idiotypic cross reactions are not usually observed except among selectively bred rabbits (18,22,24) or within an inbred strain of mice (20,21,23,25). Nisonoff and colleagues (21), however, have described strong idiotypic cross-reactions among anti-pazobenzoate antibodies from BALB/c, A, and C57BL/6 mice, though the relationship of these idiotypes to combining sites was not discussed.…”

Genetics of Restricted Antibodies to Streptococcal Group Polysaccharides in Mice

“…Since the bands of these clones A and B appear to be products of the low responder H-chain genotype, their variable regions are likely to be of C57BL/6 origin as variable and constant region genes of the H chains are closely linked (10,25,29). The absence of clones A and B in Ig ~/a F~ progeny but their occurrence in Ig bib F2 mice (Table I) points in the same direction.…”

“…idiotypic intrastrain cross-reactions of specific antibodies stimulated in A/J and BALB/c mice (24,25). Recently, Pawlak and Nisonoff (26) extended this observasion for anti-p-azo-phenylarsonate antibodies of A/J mice to closely related mouse strains, while antibodies raised in mice from unrelated strains failed to cross-react idiotypically (10,26).…”

“…The control mechanism(s) that regulate clonal propagation to yield isoelectric spectra of A-CHO antibodies of restricted heterogeneity in BALB/c mice occurs independent of the heavy-chain allotype (Table I) and is thus of a different nature than the heritable factors that determine the idiotype of mouse antibodies and the respective allotype of the strain (10,23,25,29,33). If present, this mechanism also exerts its control on antibody clones of different genetic origin such that Ig bib C57BL/6 X BALB/c F2 mice may respond with clonal isoelectric patterns typical for BALB/c mice; while, if absent, Ig ~t~ F~ progeny may show patterns as do C57BL/6 mice.…”