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J L Hurwitz

Publications and source records attributed to J L Hurwitz.

77 records · Page 5Linked to original sources
PubMed1980

CH gene rearrangements in IgM-bearing B cells and in the normal splenic DNA component of hybridomas making different isotypes of antibody.

To probe mechanisms operating at the CH gene locus during normal B lymphocyte differentiation, we have used cloned probes for the constant region genes Cmu, C gamma 1 and C alpha to analyze the immunoglobulin heavy chain genes of three kinds of cell populations in successive stages of B cell development. These are IGM-bearing B lymphocytes from the normal spleen of unprimed mice, hybridomas prepared by fusing spleen cells from antigen-primed mice with the SP2/O permanent cell line and selected to secrete one of five different isotypes (IgM, IgG3, IgG1, IgG2 and IgA) and a set of plasmacytoma lines. The IgM-bearing B cells carry Cmu genes with rearrangements between VH and JH genes on both chromosomes even though only one chromosome is expressed; clearly, allelic exclusion cannot be explained by the lack of CH gene rearrangement on the nonexpressed chromosome. The normal splenic DNA component of antibody-secreting hybridomas displays rearrangements between JH and Cmu genes as well as among CH genes other than Cmu, with concomitant deletion of CH genes 5' to those expressed. These CH rearrangements and deletions are likely to accompany the isotype switching process and may occur on both expressed and nonexpressed chromosomes. We used hybridomas (spleen-derived), which secrete primarily IgM, and plasmacytomas (gut-derived), which secrete primarily IgA, to represent plasma cells in early and late stages of differentiation, respectively. A direct comparison of hybridomas and plasmacytomas making the same products (IgG3 or IgG1) indicates that hybridomas display a low frequency (2/12) of nonexpressed C alpha gene rearrangements in contrast to the high frequency (7/10) displayed by plasma-cytomas. We propose that CH gene switching rearrangements and deletions may occur successively along the CH gene locus, involving any of the undeleted genes at each step. These can occur on both expressed and nonexpressed chromosomes during the normal clonal outgrowth of a B cell line in vivo, and would result in the accumulation of both productive and nonproductive rearrangements of the presumed last CH gene, C alpha.

B-Lymphocytes↗
PubMed1980

Successive switching of antibody isotypes expressed within the lines of a B-cell clone.

An antigen-stimulated B cell can differentiate to form a clone of cells that secrete antibodies with the IgM, IgG1, and IgA isotypes. We have examined the sequence of isotype expression by proliferating cell lines within a clone by directly staining for immunoglobulin in the cytoplasm of clonal daughter cells. All of the cones selected for analysis originally secreted IgM as well as other isotypes, as determined by radioimmunoassay of culture fluids. Cell staining showed that (i) at least 25% of the cells contained more than one isotype, indicating that cells can switch expression of isotypes during clonal expansion; (ii) some cells contained both IgM and IgA without detectable IgG1, and some cells contained both IgM and IgG1 without detectable IgA, suggesting that cells can switch from IgM directly to IgG1 or IgA; and (iii) some cells contained both IgG1 and IgA, indicating that cell lines can undergo two successive switches from IgM to the IgG1 and IgA isotypes. Using serological markers for allotypic determinants on the constant region of heavy chains, we have also shown that heterozygous B cells specific for phosphorylcholine generated clones of cells that secreted IgG1 and IgA antibodies that were derived from the expression of genes on only one parental chromosome. Assuming that the gene coding for the IgA isotype is the last gene in the gene cluster coding for heavy chain isotypes, we have proposed a model of successive, but not necessarily stepwise, switching of isotypes within B-cell lines, leading to the eventual accumulation of cells expressing IgA.

Animals↗
PubMed1976

Anatomical aspects of the superior olivary complex.

The cytology of the superior olivary complex was studied in nissl stained sections of eight human brainstems, including adult, infant and fetus, and in the brains of ten juvenile rhesus monkeys. The most prominent components of the superior olivary complex of primates were specifically investigated, i.e. the medial (SOM) and lateral (SOL) superior olivary nuclei. Cell counts of these segments were done in human brainstems. The adult SOM was comprised of an average of 11,428 (7,850--15,010) perikarya; the SOL contained an average of 3,923 (2,890--5,400) neurons. These findings indicate that the SOL contains as many cells as reported in other primates, and is not reduced. The SOL appears somewhat inconspicuous in the human because it is organized into as many as six clusters of cells rather than forming one well circumscribed configuration as in the monkey and cat. The total cell population of the SOM together with the SOL was approximately the same on each side of individual brains. If one segment was larger on one side than the opposite side, the other segment was correspondingly reduced to maintain the relative symmetry. This suggests that a single mechanism controls the cell complement of at least two segments of the superior olivary complex.

Adult↗