The genetic control of antibody variable regions in the mouse

Abstract

The genetic control of the variable (V) 1 regions of mouse antibodies is being analysed at several levels. The direct chemical analysis of V-region genes is underway [87]; antibody V-genes have been isolated from the D N A of differentiated and undifferentiated mouse cells and are now being sequenced. These studies already provide support for the conclusions based on analysis of amino acid sequences of V-regions and the genetic analysis of V-region genes using markers such as idiotype. In this chapter, we will concentrate on what has been learned from the latter kinds of studies such as the approximate size of VL and V H loci, the organization of VH genes and the relationship of V-region and C-region loci. Our purpose will be to bring to date the information on mouse V regions from a variety of sources using as a basis several recent reviews of this field by Eichmann [27], M~ikel~i and Karjalainen 1-59], Potter [74] and the summaries of the H o m o g e n e o u s Immunoglobulin Workshops [90].V-region genetic studies in the mouse owe their rapid development to two systems: the first of these is the mouse plasmacytoma developed by Michael Potter and co-workers. As Melvin Cohn points out, "The mouse system bears the stamp of Michael Potter who systematically developed the methods for provoking and characterizing mouse myelomas and who established a collection of cell lines which are to this field what the T-phages were to molecular biology" [24]. These plasmacytomas have been the source of the homogeneous antibodies used for ~-To whom offprint requests should be sent 1 Antibody structures will be abbreviated throughout this review as follows: the variable regions (V) o f heavy and light chains, VH and VL, and their constant regions, CH and CL. The structures as they relate to types of antibody subunits are abbreviated as V~c and CK (kappa chain) and VZ (lambda chain), V~c-t, etc.; VH-1, etc. (kappa or heavy chain variable region isotype), CH-y2a, etc. (heavy chain constant region isotype)The abbreviations for the gene or locus controlling these structures are for V-regions: Vh, V~c, and V2, for C regions of light chains, C~c and C2; and for heavy chains, the entire locus is designated Ch and specific genes, Ig-1 to Ig-6 according to ref. [34] 0344-4325/78/0001/0133/$ 7.40

A major crossreactive idiotype associated with human antibodies to the Haemophilus influenzae b polysaccharide. Expression in relation to age and immunoglobulin G subclass.

“…Drawing tive B cells and thus are preferentially selected and expanded. Lsive studies of other CRI systems (26)(27)(28), we Recently it has been shown that immunization of adults with -CRI defined by our anti-Id reagent is serving as Hib PS generally results in an increase in antibody avidity (31). iarker for a family of structurally related V do-An interesting group of subjects were the five adults who were rh prevalence of the CRI in an outbred popula-negative for CRI in both pre-and postimmunization sera.…”

A Three-Megabase Yeast Artificial Chromosome Contig Spanning the C57BL Mouse Igh Locus

“…The V region gene segments, Igh-V or V H , have posed a larger challenge; estimates of their numbers range from hundreds to thousands (7)(8)(9)(10). Genetic mapping experiments indicated that the locus is a centimorgan or larger (11)(12)(13), suggesting a sequence size of several million base pairs of DNA, consistent with a gene content of hundreds to thousands of coding elements. Detailed studies of the organization of V H gene families by Brodeur and colleagues (14) have provided a better understanding but much remains to be elucidated.…”

Two distinct allotypic determinants on the antigen-specific suppressor and enhancing T cell factors that are encoded by genes linked to the immunoglobulin heavy chain locus.

“…To demonstrate the genetic specificity of the BALB/c anti-CB-20 antiserum, the reactivity was investigated by the dye exclusion cytotoxic assay on thymocytes derived from various strains of mice including allotype congenic mice: (19).…”