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Raul M Torres

Publications and source records attributed to Raul M Torres.

6 recordsLinked to original sources
PubMed2006

IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection.

IL-23 induces IL-17 production in activated CD4+ T cells and participates in host defense against many encapsulated bacteria. However, whether the IL-23/IL-17 axis contributes to a Mycoplasma pneumoniae (Mp)-induced lung inflammation (e.g., neutrophils) has not been addressed. Using an acute respiratory Mp infection murine model, we found significantly up-regulated lung IL-23p19 mRNA in the early phase of infection (4h), and alveolar macrophages were an important cell source of Mp-induced IL-23. We further showed that Mp significantly increased IL-17 protein levels in bronchoalveolar lavage (BAL). Lung gene expression of IL-17, IL-17C and IL-17F was also markedly up-regulated by Mp in vivo. IL-17 and IL-17F were found to be derived mainly from lung CD4+ T cells, and were increased upon IL-23 stimulation in vitro. In vivo blocking of IL-23p19 alone or in combination with IL-23/IL-12p40 resulted in a significant reduction of Mp-induced IL-17 protein and IL-17/IL-17F mRNA expression, which was accompanied by a trend toward reduced lung neutrophil recruitment, BAL neutrophil activity, and Mp clearance. However, IL-23 neutralization had no effect on Mp-induced lung IL-17C mRNA expression. These results demonstrate that IL-17/IL-17F production is IL-23-dependent in an acute Mp infection, and contributes to neutrophil recruitment and activity in the lung defense against the infection.

Animals↗
PubMed2006

Receptor editing for better or for worse.

Receptor editing has emerged from its original identification as a minor secondary mechanism of B cell tolerance to be considered as a dominant mechanism by which autoreactive immature B cells are rendered tolerant. Clonal deletion, previously regarded as the major mechanism of central B cell tolerance, has been shown by recent studies to operate secondarily and only when receptor editing is unable to provide a non-autoreactive specificity. Receptor editing has also been shown to operate during the development of wild-type B lymphocytes, and ongoing investigations demonstrate the influence of particular signaling molecules in the induction and/or inhibition of receptor editing. Together, these studies begin to map the signaling pathways that regulate receptor editing in autoreactive and non-autoreactive immature B cells.

Animals↗
PubMed2005

Receptor editing can lead to allelic inclusion and development of B cells that retain antibodies reacting with high avidity autoantigens.

Receptor editing is a major B cell tolerance mechanism that operates by secondary Ig gene rearrangements to change the specificity of autoreactive developing B cells. In the 3-83Igi mouse model, receptor editing operates in every autoreactive anti-H-2K(b) B cell, providing a novel receptor without additional cell loss. Despite the efficiency of receptor editing in generating nonautoreactive Ag receptors, we show in this study that this process does not inactivate the autoantibody-encoding gene(s) in every autoreactive B cell. In fact, receptor editing can generate allelically and isotypically included B cells that simultaneously express the original autoreactive and a novel nonautoreactive Ag receptors. Such dual Ab-expressing B cells differentiate into transitional and mature B cells retaining the expression of the autoantibody despite the high avidity interaction between the autoantibody and the self-Ag in this system. Moreover, we find that these high avidity autoreactive B cells retain the autoreactive Ag receptor within the cell as a consequence of autoantigen engagement and through a Src family kinase-dependent process. Finally, anti-H-2K(b) IgM autoantibodies are found in the sera of older 3-83Igi mice, indicating that dual Ab-expressing autoreactive B cells are potentially functional and capable of differentiating into IgM autoantibody-secreting plasma cells under certain circumstances. These results demonstrate that autoreactive B cells reacting with ubiquitous membrane bound autoantigens can bypass mechanisms of central tolerance by coexpressing nonautoreactive Abs. These dual Ab-expressing autoreactive B cells conceal their autoantibodies within the cell manifesting a superficially tolerant phenotype that can be partially overcome to secrete IgM autoantibodies.

Age Factors↗
PubMed2005

Lsc regulates marginal-zone B cell migration and adhesion and is required for the IgM T-dependent antibody response.

The humoral immune response to protein antigens is composed of a rapid low-affinity IgM antibody response followed by an IgG response exhibiting higher affinity. Here, we demonstrate that Lsc, a protein that regulates G protein-coupled-receptor signaling and RhoA activation, is required by B lymphocytes for the antigen-specific IgM antibody response to a protein antigen. We further show that in lsc(-/-) mice, MZB cells are selectively affected such that naive and in vivo-activated MZB cells migrate toward sphingosine-1-phosphate at increased proportions but release inefficiently from integrin ligands. Consequently, lsc(-/-) MZB cells do not traffick appropriately in an immune response and do not contribute to the TD antibody response. These data demonstrate that Lsc regulates the migration and adhesion of MZB cells, and this regulation appears to be required for these cells to contribute to the antibody response to TD antigens.

Animals↗
PubMed2004

Receptor editing is the main mechanism of B cell tolerance toward membrane antigens.

Self-reactive B cells specific for ubiquitous membrane-bound autoantigens are eliminated in the bone marrow by two mechanisms of tolerance: receptor editing and clonal deletion. However, the relative contributions of clonal deletion and receptor editing to B cell tolerance in a polyclonal B cell population have not been established. Here we show that tolerance toward a membrane antigen-reactive B cell clone acts by receptor editing with very minimal cell loss. The capacity of receptor editing to rescue almost all autoreactive B cells from deletion relies on the availability of multiple joining light chain gene segments as substrate for secondary immunoglobulin light chain gene rearrangement and is independent of the affinity of the autoantigen and the presence of non-autoreactive B cells. Our data further suggest that clonal deletion is a default pathway that functions only when receptor editing has been exhausted.

Animals↗