Samuel J. Black

An immunochemical analysis of class I (BoLA) molecules on the surface of bovine cells

As in other species, bovine class I MHC molecules have been found to be cell surface heterodimers composed of a glycosylated heavy chain of approximate relative mass 44000, associated with B2m of relative mass 12000 (Hoang-Xuan et al. 1982). To date, serological definition of the BoLA system, using alloantisera, has proceeded through two international workshops (Spooner et al. 1979, Anon 1982)which have identified 17 apparent class I alleles at a single locus, BoLA-A. To gain further insights into the nature and heterogeneity of expressed bovine MHC products, we have attempted to obtain some measure of the diversity of cell surface-expressed BoLA class I molecules by establishing a structural relationship between polymorphic and monomorphic epitopes detectable on bovine class I MHC products. This was done by immunochemical analysis of detergent lysates of radiolabeled peripheral blood lymphocytes (PBL) immunoprecipitated with bovine alloantisera, mouse mAbs, and a rabbit antiserum specific for class I HLA heavy chains not complexed to B2m. BoLA typing was performed using a panel of alloantisera and monoclonal antibodies developed in our laboratory in a standard microlymphocytotoxicity assay (Teale et al. 1983). All immunochemical studies were performed with PBL of a four-year-old Boran (Bos indicus) steer, number B641. This animal is heterozygous at the BoLA-A locus with the phenotype Awl0/KN18. The KN18 specificity is defined by two alloantisera (KMA010 and KMA018) and mAb P3. The lead serum, KMA018, has a correlation coefficient with the specificity of 0.885. A population study involving more than 1600 cattle suggested that KN18 is encoded at the BoLA-A locus (Kemp 1985). Furthermore, in an extended survey of more than 2000 cattle,

Allotypes of mouse igm immunoglobulin.

GENETIC polymorphism of the structural genes encoding the class-specific (heavy) polypeptide chains of the immunoglobulin (Ig) molecules provides a useful set of markers for elucidating the arrangement and expression of these genes. On the basis of various antigenic, physiochemical and biological properties, the immunoglobulins of the mouse have been divided into eight distinct classes, IgM, IgD, IgA, IgG1, IgG2a, IgG2b, IgG3 and IgE, with a specific structural gene determining the heavy chain (H) for each class. Previous studies have documented the existence of a genetic polymorphism for five of these H-chain genes1–3, with all the genes being closely linked constituting a heavy chain chromosome region. The most recent of these loci to be demonstrated (Ig-5, determining the δ chain)3 was detected by the reaction of alloantisera prepared against spleen cells from mice differing in both H–2 and allotype. These sera reacted with B lymphocytes of the appropriate allotype congenic strains, as assessed by either immunofluorescence, or cell surface iodination and polyacrylamide gel electrophoresis (PAGE). As most B lymphocytes express cell surface IgM as well as IgD (refs 4–6), we have further pursued these various approaches to identify Ig allotypes and have found a polymorphism of the heavy chain (μ) of murine IgM, a molecule found in pentameric form (19S) in serum, and in monomeric (8S) form on the surface of lymphocytes. This defines a locus, Ig-6, which encodes the μ chain of most mouse IgM immunoglobulin.

A ROLE FOR IgD: DISSOCIATION OF MEMORY INDUCTION FROM AFFINITY MATURATION

Publisher Summary This chapter discusses the role of IgD in dissociation of memory induction from affinity maturation. Studies suggest that surface IgD receptors play a crucial role in determining the potential for affinity maturation in memory B cell populations. The increased antigen-binding capacity of memory cells with IgD receptors provides a logical explanation for how a differential sensitivity to antigen-driven selection can be maintained in early and mature memory populations. Memory cells, whether IgD + or IgD − , carry surface IgG receptors. The difficulty in detecting these receptors, however, suggests that they are represented much more sparsely on the cell surface than IgD receptors. Differentiation from IgD + to IgD must, therefore, dramatically reduce the antigen-binding capacity of a given cell even though the specificity and affinity of its receptors remains constant. This reduction is tantamount to specifically reducing the antigen concentration for cells in the mature IgD − memory population, since the probability that a cell with IgG receptors of a given affinity will capture antigen will be considerably decreased once its IgD receptors are lost. IgD receptors, then, appear to play two related roles in memory development. First, they extend the lower boundary of the affinity range of early memory B cell populations induced by a given antigenic stimulus and thus broaden the initial diversity of responses from these populations. Second, these early memory populations, so long as they persist, serve as a reservoir from which mature memory populations with higher affinities for the original or a related antigen can be drawn.

REGULATION OF ANTIBODY RESPONSES

Publisher Summary This chapter describes using the regulation of idiotype production as a context for illustration of basic circuit properties (a) a core regulatory circuit (CRC) consisting of two pairs of Ts and Th that regulate each other so that the circuit maintains stably in either the help or suppression mode; (b) a macrophage-containing auxiliary regulatory circuit (ARC) sensitive to serum idiotype levels that can switch the CRC from help to suppression; (c) a carrier-specific Th circuit that regulates the supply of idiotype-specific help; and (d) an allotype-sensitive ARC that suppresses the production of idiotypes associated with an allotypebearing IgG heavy chain. It discusses the tentative nature of the detail with which the basic circuit structures can be constructed. Existentially, the presentation of detail is inescapable since abstract concepts such as circuit design require concrete models from which essential principles can be extracted. Furthermore, detail must be included to enable design of experiments that provide grounds either for rejection of the model or for its modification to conform to reality.