877 research outputs found

    Development of T-B cell collaboration in neonatal mice

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    The neonatal immune response is impaired during the first weeks after birth. To obtain a better understanding of this immaturity, we investigated the development of T cell interactions with B cells in mice. For this purpose, we analyzed the immune response to three T-dependent antigens in vivo: (i) the polyclonal antibody response induced by vaccinia virus; (ii) the production of polyclonal and specific antibodies following immunization with hapten-carrier conjugates; (iii) the mouse mammary tumor virus superantigen (sAg) response involving an increase in sAg-reactive T cells and induction of polyclonal antibody production. After vaccinia virus injection into neonates, the polyclonal antibody response was similar to that observed in adult mice. The antibody response to hapten-carrier conjugates, however, was delayed and reduced. Injection with sAg-expressing B cells from neonatal or adult mice allowed us to determine whether B cells, T cells or both were implicated in the reduced immune response. In these sAg responses, neonatal T cells were stimulated by both neonatal and adult sAg-presenting B cells but only B cells from adult mice differentiated into IgM- and IgG-secreting plasma cells in the neonatal environment in vivo. Injecting neonatal B cells into adult mice did not induce antibody production. These results demonstrate that the environment of the neonatal lymph node is able to support a T and B cell response, and that immaturity of B cells plays a key role in the reduced immune response observed in the neonat

    Mechanisms regulating IgA class-specific immunoglobulin production in murine gut-associated lymphoid tissues. I. T cells derived from Peyer's patches that switch sIgM B Cells to sIgA B cells in vitro

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    To explore mechanisms of T cell regulation governing mucosal IgA immune response, concanavalin A-induced cloned T cell lines from Peyer's patches (PP) as well as spleen were established. The cloned cell lines expressed Thy- 1.2(+), Lyt-l(+)2(-) and were radioresistant (1,500 rad). The capacity of the cloned T cells to regulate Ig synthesis was determined by measuring their effect on lipopolysaccharide (LPS)-induced polyclonal Ig synthesis by PP B cells. In initial studies Ig secreted by B cells was determined by double antibody radioimmunoassay. LPS in the absence of cloned T cells induced abundant amounts of IgM (average 8,860 ng/2 × 10(5) B cells) and IgG (average 1,190 ng/2 × 10(5) B cells), but little or no IgA. The addition of PP cloned T cells markedly suppressed production of IgM (88 percent at the highest T/B cell ratio, 4:1), but the addition of spleen cloned T cells suppressed only a little or not at all. IgG production was inhibited by both PP and spleen T clone cells (70 percent at the 4:1 T/B ratio), wheras IgA synthesis was enhanced by both clones, but only to a limited degree. In subsequent studies the expression of class-specific surface Ig (sIg) and cytoplasmic Ig (cIg) on/in unseparated PP B cells as well as Ig class- specific PP B cells and spleen B cells during culture with or without the cloned T cells was determined by immunofluorescence. The major findings were as follows: (a) Compared with unseparated B cell cultures and cultures of purified sIgM B cells derived from PP containing LPS alone, cultures containing LPS and PP cloned T cells showed a marked decrease in cIgM-, sIgG-, and cIgG-expressing cells that was accompanied by a striking increase in sIgA-bearing, but not cIgA-containing, cells. In contrast, unseparated B cell cultures and cultures of purified sIgM B cells derived from PP containing LPS and spleen cloned T cells did not show any increase in sIgA- bearing cells. (b) Compared with purified sIgG-bearing PP B cell cultures containing LPS alone, purified sIgG-bearing PP B cell cultures containing both LPS and PP cloned T cells showed no substantial change in sIgG- or cIgG- expressing cells, and no sIgA- or cIgA- expressing cells appeared. (c) Compared with sIgA-bearing PP B cell cultures containing LPS alone, purified sIgA-bearing PP B cell cultures containing both LPS and PP cloned T cells showed no increased proliferation, and cIgA cells did not occur. Cultures of purified sIgM B cells derived from spleen containing LPS and PP cloned T cells showed qualitatively similar changes. From these results we conclude that PP cloned T cells induced class-specific switching from sIgM- to sIgA- bearing B cells, whereas spleen cloned T cells lacked this property, although they may have induced an IgM {arrow} IgG or intersubclass IgG switch. These processes seem to be in part tissue dependent. Furthermore, the PP switch T cells appear to operate as true switch cells, which govern the pathway of DNA recombination events, rather than as classical helper cells, which act to expand already differentiated cells. Finally, these switch T cells probably account for the fact that PP are an important source of IgA B cells and also a major site of IgA heavy chain class switching during gut-associated mucosal B cell proliferation and differentation

    B cell differentiation in sheep

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    The ileal Peyer's patch (IPP) of lambs is a region of intense lymphopoiesis and B cell development. Monoclonal antibodies against ovine lymphocyte antigens have been used to characterise the IPP lymphocyte. Three murine monoclonal antibodies against ovine IgM, IgGi and Ig light chain were produced and are described fully. IgM and MHC class II antigens are expressed on the vast majority of IPP cells whilst cells bearing other serum Ig isotypes and T cell antigens are rare. A novel Ig molecule appears to be coexpressed with IgM, it is proposed that this is the ovine equivalent of IgD.The ileal Peyer's patch (IPP) of lambs is a region of intense lymphopoiesis and B cell development. Monoclonal antibodies against ovine lymphocyte antigens have been used to characterise the IPP lymphocyte. Three murine monoclonal antibodies against ovine IgM, IgGi and Ig light chain were produced and are described fully. IgM and MHC class II antigens are expressed on the vast majority of IPP cells whilst cells bearing other serum Ig isotypes and T cell antigens are rare. A novel Ig molecule appears to be coexpressed with IgM, it is proposed that this is the ovine equivalent of IgD.IPP cells can be induced to proliferate and differentiate when cultured with lipopolysaccharide (LPS) and interleukin 2 (IL2). Proliferation is inhibited by rabbit anti-sheep Ig antibodies. Using an ELISA for Ig, it has been posible to quantitate Ig synthesis and secretion. Mean cellular Ig increases greater than 25-fold during differentiation. High-rate secretion begins 4 days after initiation of culture and is virtually complete by day 7.As IPP B cells differentiate to IgM secretion, membrane Ig is rapidly lost so that by day 6, only 15% of cells express Ig en their surfaces. Changes in MHC class II antigens were also studied. Surface expression of MHC class II molecules doubled by 24 hours and slowly declined to resting levels as differentiation proceeded. A large increase in cytoplasmic MHC class II content was noted on day 3. The reasons for this inci-ease are discussed
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