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J J Cebra

Publications and source records attributed to J J Cebra.

139 records · Page 8Linked to original sources
PubMed1966

Rabbit lymphoid cells differentiated with respect to alpha-, gamma-, and mu- heavy polypeptide chains and to allotypic markers Aa1 and Aa2.

Lymphoid cells present in spleen and lymph nodes of hyperimmune rabbits were found to be differentiated with respect to the class of immunoglobulin heavy chain which they contained. The relative proportions of cells containing the various heavy chains were as follows: alpha-chain (5 to 8%), micro-chain (14 to 21%), and gamma-chain (71 to 81%). The allotypic markers Aa1 and Aa2, found on heavy chains, were also found to be separately localized in cells of Aa(1)/Aa(2) heterozygous rabbits. The ratio of cells in spleen and lymph nodes containing the Aa1 marker to those containing the Aa2 marker varied with individual rabbits; the range was 53 to 88% Aa1 versus 12 to 47% Aa2.

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The secretory IgA system of the gut.

Most commonly, humoral immunity manifested in the gastrointestinal tract of mammals is due to the presence of secretory IgA antibodies. Antibody specificities have been detected in the secretory IgA of gut secretions to a wide range of naturally occurring viral and bacterial components and to test antigens such as chemically modified proteins. Much of the IgA found in gut secretions is synthesized and secreted locally by the abundant plasma cells of the lamina propria. Development of methods for establishing local protective immunity in the gut requires knowledge of the origins of these plasma cells and of the whereabouts of their precursors when they are susceptible to antigen-driven proliferation and/or maturation. The Peyer's patches have been shown to contain a population of B lymphocytes especially rich in precursors for IgA plasma cells and in cells which can repopulate gut lamina propria with such IgA plasma cells. The Peyer's patches also appear to 'sample' gut antigens, in that small amounts of antigens are passed intact through their dome epithelial cells. Recent experiments bearing on the origins, differentiation and maturation, antigen sensitivity, migration and lodging of precursors for gut IgA plasma cells are discussed. We use the following three systems: (1) congenic transfer of cells from different murine lymphoid cell sources or mixtures of these (CB20 leads to BALB/c or BALB/c leads to CB20) and the use of allo-antisera to IgA allotypic determinants to assess their potential to impart an adoptive IgA antibody response to the recipient and to repopulate its histocompatible lamina propria with IgA plasma cells; (2) clonal precursor analysis (the method of Klinman) both to enumerate antigen-sensitive cells in different tissues of mice and to evaluate their potential to generate plasma cells making particular isotypes and idiotypes of antibodies; (3) use of pairs of Thiry-Vella loops in rabbits, each member either bearing or lacking a Peyer's patch, and quantitation of antibodies of each isotype and of total secretory IgA to assess the response of each loop with the time after local immunization. The results from all three systems provide strong evidence for the importance of Peyer's patches in supplying cells responsible for local humoral immunity and suggest both a differentiative pathway for IgA precursors and their whereabouts when antigen may cause the expansion of a population of specific cells.

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Reoviruses as probes of the gut mucosal T cell population.

Reovirus, serotype 1, causes a transient, asymptomatic infection of the murine intestine when given intraduodenally or orally. However, this infection markedly perturbs both B- and T- cell populations in Peyer's patches (PP) resulting in: 1) a rapid and persistent increase in specific precursors for cytotoxic T cells (pCTL) and a gradient of frequencies highest in PP and lowest in distal lymphoid tissue; 2) a similar increase in memory B cells committed to IgA; 3) the transient appearance of a subset of germinal center B cells identified by MAb, GC-T; 4) the appearance of pCTL among intraepithelial lymphocytes; and 5) the antigen non-specific alteration in Ig isotype potential of B cells previously primed and found in PP. The pCTL appearing upon acute gut mucosal infection with reovirus are Thyl+, Lyt2+, virus-specific, viral serotype non-specific, class I MHC haplotype restricted and occur within the subset of T cells which newly appears also identified by MAb GC-T. Infections of both neonatal and severe-combined immunodeficient mice indicate that the elements of the immune system may operate at many levels to resist, limit, contain, and resolve viral infection.

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PubMedDate not supplied

Intraepithelial lymphocytes contain virus-specific, MHC-restricted cytotoxic cell precursors after gut mucosal immunization with reovirus serotype 1/Lang.

Reovirus 1 has been intraduodenally administered to mice to determine whether virus-specific cytotoxic cells can be elicited within the intestinal epithelium. We have found that reovirus-stimulated, but not control mice, generate virus-specific cytotoxic effector cells when isolated intraepithelial lymphocytes are restimulated in vitro. These effector cells are restricted by major histocompatibility complex (MHC) class I determinants and thus appear to utilize the T cell antigen receptor and to be of the T cell lineage. These results raise the possibility that cytotoxic T lymphocytes (CTL) may be an important component of the host immune response in the intestinal epithelium.

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PubMedDate not supplied

Intraduodenal application of cholera holotoxin increases the potential of clones from Peyer's patch B cells of relevant and unrelated specificities to secrete IgG and IgA.

Although it has been established that cholera toxin is both an effective mucosal immunogen and adjuvant, the mechanism by which it acts has not been determined. The relative contributions of the pharmocologic and binding capacities of holotoxin have been assessed by comparing holotoxin, acid dissociated B subunit, and B subunit from the Texas Star variant, which is deficient in production of the A subunit, for their ability to generate toxin-specific precursors in vivo that give rise to clones secreting exclusively IgA in vitro. In this way we demonstrated that although B subunit is as immunogenic as the holotoxin, pharmacologic activity appears to play a role in the generation of IgA-committed precursors. In addition, intraduodenal (i.d.) application of holotoxin can act to alter the isotype display of previously primed B cells in Peyer's patches (PP) specific for a chemically unrelated hapten resulting in an increase in the proportion of their clones that secrete IgA or IgG and a decrease in the proportion that secrete IgM following antigen-dependent in vitro clonal expansion. Intraduodenal application of cholera toxin did not appear to nonspecifically increase the proportion of IgA-committed precursors as judged by staining for sIgA and mRNA alpha levels. However, following i.d. application of cholera toxin, an overall downward shift in the levels of sIgD and s kappa was observed in the PP B cell population. We suggest that the holotoxin can nonspecifically affect the isotype display of PP B cells by altering their responsiveness to the stimuli present in the in vitro cultures.

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