SHIV SUBRAMANIAM PILLAI

..Siglecs modulate immune responses, influencing almost every cell in the immune system, and are of relevance both in health and disease...

..Although immature B cells can mature into follicular B cells in this niche as well as in the spleen, the lineage commitment event that accompanies positive selection of B cells occurs only in the spleen...

..Here, we discuss the functions of these cells in both innate and adaptive immunity. We also attempt to reconcile differing viewpoints regarding the generation and function of marginal zone B cells in rodents and primates...

..A study in this issue of the JCI reveals, quite unexpectedly, that IRE1 is also required early in B lymphocyte development for the induction of the machinery that mediates Ig gene rearrangement...

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..This cell fate decision could provide mechanistic insights that are relevant to other commitment events in lymphocytes...

..Current information on tolerance checkpoints in B cells, B cell depletion, BAFF blockade, regulatory B cells and clonal ignorance mediated by the SIAE/Siglec pathway will be reviewed...

..9 in subjects with type I diabetes. Functionally defective SIAE rare and polymorphic variants represent a strong genetic link to susceptibility in relatively common human autoimmune disorders...

..These results describe a novel catalytic regulator of B cell signaling and underscore the crucial role of inhibitory signaling in the maintenance of immunological tolerance in the B lineage...

..These studies provide in vivo evidence for a genetic interaction between the Notch and NF-kappaB pathways...

..Taken together, these data demonstrate that the loss of this RIP-family kinase does not compromise B lymphocyte development and maintenance, but leaves open the possibility that PKK may have a redundant role in these processes...

..Differences in antigen-receptor signal strength may determine whether B cells assume a marginal zone, follicular or B-1 phenotype...

..These studies suggest that PKK may be required early in B cell development and for BCR-mediated B cell proliferation...

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..The bone marrow represents a unique type of secondary lymphoid organ in which mature B cells are strategically positioned in the path of circulating microbes...

..Taken together, these data indicate that PKK may function in both a kinase-dependent as well as a kinase-independent manner to activate NFkappaB...

..These data suggest that newly formed B cells mature into IgD(hi) B cells simultaneously in the spleen and the bone marrow and establish in a stringent manner that humoral immune responses can be initiated in situ in the bone marrow...

..Moreover, using this previously unknown migratory pathway, antigen-pulsed DCs were able to trigger central memory T cell-mediated recall responses in the bone marrow...

..Peripheral B cells exhibited circumscribed defects in anti-IgM induced protein tyrosine phosphorylation, which may contribute to the unexpected proliferative defect seen in these cells...

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..We suggest that in these mice, receptor editing functioned to lower the affinity for self-Ag below a threshold that would result in overt pathology, while allowing development of low affinity anti-self Abs...

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..These results describe the existence of an alternative pathway of B cell maturation in the periphery that gives rise to a tissue-specific B cell subset...

..These two follicular populations exhibit differences in basal tyrosine phosphorylation and in BCR-induced proliferation, suggesting that they may represent functionally distinct populations of long-lived recirculating B cells...

..These results suggest that CD9 is dispensable for B cell development and humoral immunity, but that this protein may serve as an additional marker for the presumed MZ precursor population of splenic B cells...

..Insights obtained may be of importance in leukemias and in autoimmune diseases like lupus. ..

..The actual oligomeric structure of the enzyme will be determined and the possibility that mutations function in a dominant negative manner will be examined in cell line based studies. ..

..The gene that codes for an enzyme that controls the strength of the immune response will be studied. This gene may be an important target for the treatment of lupus and other related diseases. ..

..PKK represents a novel enzyme that may be critical in pathways that are important in cancer, inflammation, cell survival, and differentiation. ..

..Insights obtained may be of importance in leukemias and in autoimmune diseases like lupus. ..

..A novel strategy for HIV vaccination is proposed, that may permit the induction of protective neutralizing antibodies. ..

..Since the majority of human lymphomas develop form activated B-cells, these signaling mechanisms are likely to be of direct relevance for a significant proportion of human cancers. ..

..Finally we will attempt to determine whether antigen-specific MZ B cells, as opposed to follicuar B cells, can readily capture and present blood borne antigens, and thus activate na'fve T cells. ..

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