Joan L. Press

The B Cell Specificity Repertoire: Its Relationship to Definable Subpopulations

During the years since Burnet (1959) presented the Clonal Selection Theory of Acquired Immunity as the basis of immtinologic specificity, the major tenets have been tested and found to be essentially correct. Definitive experiments have supported (a) the limited or unique potentiahty of antibody forming cell precursors (B cells) at a given point in time (Klinman 1969, 1971b, c, 1972, Bosma & Weiler 1970, Marchalonis & Nossal 1968, Luzzati et al. 1973); (b) the maintenance of the stimulated B cells clonotype (unique individual antibody specificity) in both the antibody forming cell progeny and in subsequent generations of secondary precursor cells (Klinman 1972, Askonas et al. 1972); (c) the identity of specificity of the B cells surface antigen receptor and its potential antibody product (Cosenza & Kohler 1972, Eichmann 1974, Pawlak et al. 1973); and (d) the uniqueness of the B cells receptor (Raff et al. 1973). Although contradictory data exist for several of these points (Cunningham & Pilarski 1974a, b, c, Couderc et al. 1973), such contradictions appear the exception rather than the rule. Given, therefore, that there exists a vast repertoire of precursor cells, each with a single, unique potential antibody product, and that the identity of cell receptor to this antibody product allows specific interaction with antigen, it would appear a simple matter to generate a plethora of highly specific antibody populations, particularly in the context of potential overlaps in antigen recognition by clonotypes, as proposed by Talmage & Cohen

Genetic and Functional Analysis of the Ia Antigens: Their Possible Role in Regulating the Immune Response

Since the initial discovery of /-region associated (Ia) antigens in the mouse (David et al. 1973, Gotze et al. 1973, Hauptfeld et al. 1973, Sachs & Cone 1973, Hammerling et al. 1974), a large amount of information has been obtained about the antigenic specificity, tissue and cellular distribution, chemistry, and potential function of this class of alloantigens (Klein 1975, Shreffler & David 1975). The /-region of the major histocompatibility complex is now subdivided into at least two regions which appear to contain the structural genes coding for several cell-surface glycoproteins found predominantly on B lymphocytes. Although Ia molecules controlled by this chromosomal segment are heterodisperse with respect to molecular weight, the degree of their structural heterogeneity has not been fully assessed. Evidence from many diJB̂ erent types of experiment indicates that these antigens are involved in T-cell-B-cell-macrophage interactions; are responsible for stimulation in mixed lymphocyte culture; and are constituents of a bewildering v£iriety of lymphocyte-derived, antigen-specific and -nonspecific factors which appear to both suppress and potentiate the immune response (Katz & Benacerraf 1976). Despite this wealth of information, the precise role of Ia antigens in

Serological characterization of a nervous system/sperm antigen (ns-52): demonstration of its presence on murine preimplantation embryos.

Abstract Anti-NS-5 antiserum raised in C3H.SW/Sn mice against cerebellum of 4-day-old C57BL/6J mice could be shown to recognize two cell surface antigens on cerebellar cells, NS-5 1 and NS-5 2 , the latter antigen being shared with mouse and rat but not rabbit sperm. An antigen operationally identical to NS-5 2 was detected using indirect immunofluorescence staining on mouse preimplantation stages of development. While the unfertilized ova did not express detectable antigen on the cell surface, the fertilized egg expressed antigen shortly before the first cleavage division. From that stage onward, the anti-NS-5 antiserum stained the blastomeres of all stages, including the trophoblast cells and inner cell mass cells of the blastocyst. No difference in staining activity was observed for preimplantation embryos of various mouse strains analyzed: C57BL/6J, BALB/c, 129/J, C3H/DiSn, CKB × BALB.K, C3H.SW/Sn, and Swiss Webster mice. The staining activity was removed when the antiserum was preabsorbed with cerebellum or sperm from any of these mouse strains or with cerebellum and sperm of rats. Lymphocytes, thymocytes, liver, kidney, and skeletal muscle from early postnatal and adult mice and heart from early postnatal mice did not absorb the staining activity and neither did rabbit sperm nor cerebellum.

IR-1A GENE INFLUENCE ON CHIMERIC LYMPHOID CELL INTERACTIONS

An adoptive cell transfer system was used to examine the capacity of (T,G)-A--L primed spleen cells from (BALB.K x BALB.B)F 1 or BALB.B BALB.K bone marrow cell chimeric mice to collaborate with DNP-primed B cells from Ir-1A high-responder (BALB.B) or low-responder (BALB.K) mice in the secondary response to DNP-(T,G)-A--L. DNP-specific antibody detectable by a modified Farr assay was produced by high-responder but not by low-responder genotype B cells when transferred with F 1 or chimeric carrier-primed spleen cells. Production of anti-DNP antibody by recipients of low-responder genotype DNP-primed B cells and (T,G)-A--L primed F 1 or chimeric spleen cells could be detected by an antigen-coated plate assay, but this anti-DNP antibody population appeared to be qualitatively different from that produced by recipients of high-responder genotype DNP-primed B cells. An allotype-specific and (T,G)-A--L antigen-specific plate assay was used to discriminate the anti-(T,G)-A--L antibodies produced by chimeric mice differing both for Ig allotype and for Ir-IA genotype. These chimeric mice did not produce anti-(T,G)-A--L antibody of low-responder allotype in amounts greater than those produced by low-responder control mice.