Segregation at a locus determining an immunoglobulin genetic marker for the light chain variable region affects inheritance of expression of an idiotype

Abstract

Idiotypic specificity can also serve as a V-region genetic marker. This is the case when a shared idiotype is present on some of the antibodies made in response to an antigen in nearly all mice of one or more inbred strains but not in other strains.Idiotypic specificities have been localized to V regions (5, 6), and a number of genetic studies with inbred mice have demonstrated linkage between genes governing idiotype and CH region allotypes (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Genetic recombination between genes governing idiotype and allotype has been reported (14-17). In the system used in the present studies, an idiotype that appears in antibodies to the p-azophenylarsonate hapten (anti-Ar antibodies) of all A/J mice (20) is also expressed by the AL/N strain (7), which has a CH-allotype similar to but distinct from that of strain A/J (21). The C.AL-20 strain, which possesses the CH region allotype of AL/N on the genetic background of the idiotype-negative (Id-) BALB/c strain, is idiotype-positive (Id+), demonstrating the linkage of idiotype with allotype (7).Results that suggest linkage of idiotype solely with CH region allotype are paradoxical, because the light (L) chain is known to be required for expression of all such idiotypes tested to date (including the anti-Ar idiotype of A/J mice) (e.g., refs. 22 and 23), and the genes governing H and L chain expression are thought to be unlinked in man (24), rabbit (25,26), and mouse (see below). A possible explanation for these results is that the various inbred strains employed in these studies possess similar or identical VL region repertoires while differing with respect to their VH region repertoires.Data consistent with this explanation were provided by the observation that L chains from normal serum IgG of most inbred strains of mice gave identical patterns of cysteine-containing peptides when analyzed by tryptic peptide mapping (27). However, such peptide maps of L chains obtained from four inbred strains (AKR/J, C58/J, PL/J, and RF/J) were distinct from those of all other mice tested, and amino acid sequence analysis of the cysteine-containing peptides unique to L chains from these strains indicated that they were derived from the V region of the K L chain (VK).

Variable region genes for the immunoglobulin framework are assembled from small segments of DNA—A hypothesis

“…Because recent studies show the apparent linkage of idiotype (which is related closely to the CDR) to allotype to be dependent in the mouse upon the light chain (54), this association becomes essentially a regulatory phenomenon and would not necessarily provide any insight into the location of the CDR or even the FR in relation to the C-region of the genome. Previous findings (55) of an identical CDR1 in a human VII and a human VAV although they differ at 21 positions throughout the V-region and an identical CDR3 (31) in a human VKI and a human VJIII despite 30 amino acid differences in the V-region also strongly support the assembly of the V-region by the joining with or insertion of the CDR and the FR pieces (1).…”

“…4). In the V-region of heavy chains (VH), the FR are 1-30, 36-49, 66-94, and 103-113 and CDR1, CDR2, and CDR3 are residues 31-35B, [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65], and 95-102; CDR1, CDR2, CDR3, and FR3 may also have insertions (cf. 2).…”

Alloantigen-specific idiotype-bearing receptors on mouse T lymphocytes. I. Specificity characterization and genetic association with the heavy-chain IgG allotype.

“…However, despite this exclusive linkage to heavy-chain allotype genes, light chains are known to play an important role in the tertiary structure of the idiotypic determinants (4,6,23,33). The involvement of light chain in the presently described Id(s) is not known, but our study has clearly established a strong association of the rabbit-5,936-antiserum-defined Id present on 7S IgG anti-CBA antibodies to the Ig-1 b or Ig-1 e heavy-chain allotype genes (Table IV) (Table V).…”

Mechanisms of regulation of cell-mediated immunity. III. The characterization of azobenzenearsonate-specific suppressor T-cell-derived-suppressor factors.

“…Because the cross-reactive idiotype may be reflective of a germ-line gene product, an analysis of ABA-specific T cells (suppressor, helper, or effector) or the ABA-specific SF might allow structural comparisons to CRI bearing Ig as has been done in other systems (28)(29)(30). This comparison is facilitated by the availability of well-characterized anti-idiotype antisera (25,27,(31)(32)(33)(34)(35).…”