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J L Press

Publications and source records attributed to J L Press.

31 records · Page 2Linked to original sources

Functional and genetic analysis of Ia antigens.

Using negative selection with anti-Ia serum and complement, Ia-"negative" lymphocyte populations give rise to clonal progeny which produce only IgM antibody, whereas Ia-positive lymphocytes generate B-cell progeny which produce IgG or both IgM and IgG antibody. The responder cell in the mixed lymphocyte reaction and the precursor and effector cells in cell-mediated lympholysis appear to be Ia-"negative" lymphocyte subpopulations. Helper T cells in some system are Ia-positive, and allotype suppressor T cells are also Ia-positive. Allogenic effect factor produced in the usual manner functions as an antigen nonspecific helper factor for several different H-2 haplotypes. However, when allogenic effect factor is produced from a mixed lymphocyte culture between responder lymphocytes treated with anti-Ia and complement and irradiated stimulator lymphocytes treated with anti-Thy-1.2 and complement, this "restricted" AEF is sharply restricted in the haplotypes it can stimulate. "Restricted" AEF produced in this manner with B10.BR responder cells and B10.S stimulator cells helps B10.S T-cell-depleted, hap-ten-primed spleen B cells but does not help B10.BR spleen cells. This raises the possibility that the Ia antigens in AEF may be derived from the stimulator B cells and/or macrophages rather than from the responder T cells.

Animals↗

Expression of Ia antigens on hapten-specific B cells. I. Delineation of B-cell subpopulations.

The nonimmune adult spleen contains at least two B-cell subpopulations. The majority of primary B cells express cell surface Ia determinants and have the capacity to give rise to IgG antibody-producing clones after T-cell dependent antigenic stimulation. There is also a small subpopulation of primary B cells which are, by definition, Ia negative, since their activity is not eliminated by negative selection with anti-Ia serum and complement. The Ia-negative B cells give rise to clones that produce only IgM antibody. These B-cell subsets may form a continuum in B-cell maturation, or they may exist as discrete B-cell lineages. Since the cellular expression of Ia antigens appears to correlate with the ability of the B cell to generate IgG-producing clones, it is speculated that Ia molecules may have a role in the IgM to IgG B-cell switch mechanism.

Animals↗

Central nervous system antigen (NS-5) and its presence during murine ontogenesis.

An antiserum raised by immunization of C3H.SW/Sn mice with cerebellum from 4-day-old C57BL/6J mice recognizes a cell surface component(s) [NS-5] present in different degrees on various parts of the mouse central nervous system. When analyzed by an antiserum- and complement-mediated cell cytotoxicity test and by the ability of various tissuesto absorb anti-NS-5 antiserum activity, the antigen(s) was detectable on cerebellum, retina, olfactory bulb, cortex, basal ganglia, and medulla but not on nonneural tissues with the exception of mature spermatozoa and 4-day-old kidney. The antigen(s) detected by the anti-NS-5 antiserum was found in similar quantities on young and adult rat and mouse cerebellum; however, it was not detectable on any of 16 clonal cell lines derived from the rat central nervous system. During preimplantation stages of murine development, the antigen could be detected on all cells of (2-4)-cell and (8-16)-cell stages and on the trophoblastic cells of blastocysts by indirect immunofluorescence, Embryos on day 9 of gestation, the earliest tested after implantation, expressed the antigen(s), but expression was restricted to the nervous system.

Animals↗

The characterization fo the B-cell repertoire specific for the 2,4-dinitrophenyl and 2,4,6-trinitrophenyl determinants in neonatal BALB/c mice.

The (B-cell) repertoire responsive to the DNP and TNP haptenic determinants in BALB/c neonates was analyzed in terms of the specificity of stimulation of neonatal B cells as well as the diversity of specificities available in neonatal populations. The results indicate that the parameters of stimulation of neonatal B cells are similar to those of nonimmune adults, particularly in the exquisitely specific stimulatory process which readily discriminates between haptens as closely related as 2,4-dinitrophenyl (DNP) and 2,4,6-trinitrophenyl (TNP). The clonotypes of monoclonal anti-DNP and anti-TNP antibodies derived from isolated neonatal BALB/c splenic B cells in fragment culture were analyzed by isoelectric focusing. During the first 4 days of neonatal life almost all of the anti-DNP-specific clones were of clonotypes displaying IgM antibodies with pI's of 5.05, 5.25, or 5.55. These could be distinguished from clonotypes responding to TNP which were also predominantly of three distinct pI's, 5.00, 5.15 or 5.40. These clonotypes, which represent the vast majority of the DNP- and TNP-specific antibody capability during the first 4 days of life, represented less than half of the clones by day 6 and were a small minority by day 9. The observation that individual 1--4-day-old donors had many B cells representative of a given predominant clonotype is evidence for cellular precommitment of specificity and indicates that clones of precommitted B cells exist as the products of normal, antigen-independent, generative processes. The observation of frequently recurring clonotypes in inbred neonates attests to the "germ line" origin of these clonotypes; however, variance in the occurrence of these clonotypes from donor to donor implies a random element in their expression. The finding that several clonotypes occur repeatedly in high numbers early in neonatal development, while other clonotypes occur only sporadically at early times, has been interpreted as a reflection of a sequential ontogenic expression of clonotypes. Thus the DNP- and TNP-specific clonotypes which predominate in neonates may be seen as representative of a total of 5,000-10,000 clonotypes which are expressed as early as the 15th to 17th day of gestation while most clonotypes appear after the 18th day of gestation.

Age Factors↗

Expression of specific clones during B cell development.

The expression of DNP- and TNP-specific B cells in spleens of neonatal BALB/c mice was analyzed by the in vitro splenic focus technique. B cells of these specificities were found to be present in slightly higher frequency in neonatal than in adult spleens. The parameters of stimulation of neonatal B cells were similar to those of adult B cells but the antibody-forming cell progeny of neonatal B cells produce predominantly gammaM rather than gammaG antibody and produce less antibody than the progeny of adult B cells. Isoelectric focusing analyses of monoclonal antibodies derived from neonatal B cells stimulated in vitro with DNP or TNP revealed that over 90 per cent of the antibodies could be identified as belonging to one of six predominant clonotypes, three specific for DNP and three for TNP. While individual neonates rarely expressed all of the predominant clonotypes, B cells of each of the six clonotypes were found in several donors. When B cells of a given predominant clonotype were present in an individual many such B cells could be found and in many cases the entire DNP- or TNP-specific B cell population of an individual could be accounted for by B cells of a single clonotype. These findings are discussed in terms of the diversity of clonotype specificities available in neonates, the kinetics of development of cells within a clonotype, and factors that may play a role in controlling the expression of B cell clones.

Amino Acid Sequence↗

Overlap stimulation of primary and secondary B cells by cross-reacting determinants.

Experiments were carried out to test the validity of the hypothesis that postulated differences in the nature of the antigen receptors of primary and secondary B cells should be reflected in a greater specificity in primary B-cell stimulation (2). Enumeration of clonal precursors stimulated by either DNP-Hy, TNP-Hy, or a mixture of both antigens confirmed this hypothesis. Since the sum of primary B cells stimulated by DNP-Hy and TNP-Hy is approximately equal to the number stimulated by a mixture of both, overlap stimulation of primary B cells by these antigens could be considered negligible. In contrast, the stimulation of B cells from mice previously immunized with DNP-Hy showed extensive overlap of stimulation by DNP-Hy and TNP-Hy. Thus secondary B cells appear less fastidious in their affinity requirements for stimulation than primary B cells.

Animals↗

Monoclonal production of both IgM and IgG1 antihapten antibody.

The anti-DNP antibodies produced by primary and secondary splenic foci were analyzed for heavy chain class by a radioimmunoassay, using iodinated, purified goat antimouse micro-chain antibody and goat antimouse gamma1 chain antibody. The frequency of primary and secondary foci producing both IgM and IgG1 anti-DNP antibody (16% and 14%, respectively) was considerably higher than that which would be predicted by a random distribution. It would thus appear that IgM and IgG1 antibody can be made by the clonal progeny of a single precursor cell.

Animals↗