361 research outputs found
Enhanced auto-antibody production and Mott cell formation in FcÎŒR-deficient autoimmune mice
Characterization of FcÎŒR deficiency in lupus-prone mic
Normal pre-B cells express a receptor complex of mu heavy chains and surrogate light-chain proteins.
Childrenâs Perception of Cancer and Survivors After a Cancer Education Program Engaging with Survivors: A Qualitative Study
Background: In Japan, cancer education utilizing external lecturers are being promoted as part of cancer control measures. The objective of this study was to clarify childrenâs perceptions of cancer and survivors and their awareness of actions for early prevention and detection of cancer after participating in a cancer education program engaging with survivors.Methods: This study was conducted during January and March 2020, using the qualitative analysis method. Homeroom teachers gave a lesson on cancer to sixth-grade students (n=69) at an elementary school in Japan. Two weeks later, a cancer survivor gave a follow-up class. Then an inductive content analysis was conducted on the content of the post-class reflection worksheets written by students.Results: After analyzing the worksheets of 59 students, they learned that âto reduce the risk of developing cancer, one should lead a healthy lifestyleâ and âstrive for early detection through cancer screeningâ through the education program. As things they can do themselves in the future, they listed âencourage family members to get cancer screenings,â âquit smoking,â and âcut back on alcohol.â In addition, children have deepened their understanding of cancer survivors and learned the importance of their own and othersâ lives.Conclusion: The results suggested that children gained practical knowledge about cancer through the program and deepened their understanding of cancer and survivors by directly interacting with and listening to survivors
Identity of the elusive IgM Fc receptor (FcÎŒR) in humans
Although Fc receptors (FcRs) for switched immunoglobulin (Ig) isotypes have been extensively characterized, FcR for IgM (FcÎŒR) has defied identification. By retroviral expression and functional cloning, we have identified a complementary DNA (cDNA) encoding a bona fide FcÎŒR in human B-lineage cDNA libraries. FcÎŒR is defined as a transmembrane sialoglycoprotein of âŒ60 kD, which contains an extracellular Ig-like domain homologous to two other IgM-binding receptors (polymeric Ig receptor and Fcα/ÎŒR) but exhibits an exclusive FcÎŒ-binding specificity. The cytoplasmic tail of FcÎŒR contains conserved Ser and Tyr residues, but none of the Tyr residues match the immunoreceptor tyrosine-based activation, inhibitory, or switch motifs. Unlike other FcRs, the major cell types expressing FcÎŒR are adaptive immune cells, including B and T lymphocytes. After antigen-receptor ligation or phorbol myristate acetate stimulation, FcÎŒR expression was up-regulated on B cells but was down-modulated on T cells, suggesting differential regulation of FcÎŒR expression during B and T cell activation. Although this receptor was initially designated as Fas apoptotic inhibitory molecule 3, or TOSO, our results indicate that FcÎŒR per se has no inhibitory activity in Fas-mediated apoptosis and that such inhibition is only achieved when anti-Fas antibody of an IgM but not IgG isotype is used for inducing apoptosis
Collision free region determination by modified polygonal\ud Boolean operations
Cutting and packing problems are found in numerous industries such as garment, wood and shipbuilding. The collision free region concept is presented, as it represents all the translations possible for an item to be inserted into a container with already placed items. The often adopted nofit polygon concept and its analogous concept inner fit polygon are used to determine the collision free region. Boolean operations involving nofit polygons and inner fit polygons are used to determine the collision free region. New robust non-regularized Boolean operations algorithm is proposed to determine the collision free region. The algorithm is capable of dealing with degenerated boundaries. This capability is important because degenerated boundaries often represent local optimal placements. A parallelized version of the algorithm is also proposed and tests are performed in order to determine the execution times of both the serial and parallel versions of the algorithm.CNPqFAPES
Augmented TLR9-induced Btk activation in PIR-Bâdeficient B-1 cells provokes excessive autoantibody production and autoimmunity
Pathogens are sensed by Toll-like receptors (TLRs) expressed in leukocytes in the innate immune system. However, excess stimulation of TLR pathways is supposed to be connected with provocation of autoimmunity. We show that paired immunoglobulin (Ig)-like receptor B (PIR-B), an immunoreceptor tyrosine-based inhibitory motifâharboring receptor for major histocompatibility class I molecules, on relatively primitive B cells, B-1 cells, suppresses TLR9 signaling via Bruton's tyrosine kinase (Btk) dephosphorylation, which leads to attenuated activation of nuclear factor ÎșB p65RelA but not p38 or Erk, and blocks the production of natural IgM antibodies, including anti-IgG Fc autoantibodies, particularly rheumatoid factor. The autoantibody production in PIR-Bâdeficient (Pirbâ/â) mice was further augmented in combination with the Faslpr mutation, which might be linked to the development of autoimmune glomerulonephritis. These results show the critical link between TLR9-mediated sensing and a simultaneously evoked, PIR-Bâmediated inhibitory circuit with a Btk intersection in B-1 cells, and suggest a novel way toward preventing pathogenic natural autoantibody production
Functional Roles of the IgM Fc Receptor in the Immune System
It is now evident from studies of mice unable to secrete IgM that both non-immune ânaturalâ and antigen-induced âimmuneâ IgM are important for protection against pathogens and for regulation of immune responses to self-antigens. Since identification of its Fc receptor (FcÎŒR) by a functional cloning strategy in 2009, the roles of FcÎŒR in these IgM effector functions have begun to be explored. Unlike Fc receptors for switched Ig isotypes (e.g., FcÎłRs, FcΔRs, FcαR, Fcα/ÎŒR, pIgR, FcRn), FcÎŒR is selectively expressed by lymphocytes: B, T, and NK cells in humans and only B cells in mice. FcÎŒR may have dual signaling ability: one through a potential as yet unidentified adaptor protein non-covalently associating with the FcÎŒR ligand-binding chain via a His in transmembrane segment and the other through its own Tyr and Ser residues in the cytoplasmic tail. FcÎŒR binds pentameric and hexameric IgM with a high avidity of ~10 nM in solution, but more efficiently binds IgM when it is attached to a membrane component via its Fab region on the same cell surface (cis engagement). Four different laboratories have generated Fcmr-ablated mice and eight different groups of investigators have examined the resultant phenotypes. There have been some clear discrepancies reported that appear to be due to factors including differences in the exons of Fcmr that were targeted to generate the knockouts. One common feature among these different mutant mice, however, is their propensity to produce autoantibodies of both IgM and IgG isotypes. In this review, we briefly describe recent findings concerning the functions of FcÎŒR in both mice and humans and propose a model for how FcÎŒR plays a regulatory role in B cell tolerance
Negative Regulation of FcΔRI-mediated Degranulation by CD81
Signaling through the high affinity receptor for immunoglobulin E (FcΔRI) results in the coordinate activation of tyrosine kinases before calcium mobilization. Receptors capable of interfering with the signaling of antigen receptors, such as FcΔRI, recruit tyrosine and inositol phosphatases that results in diminished calcium mobilization. Here, we show that antibodies recognizing CD81 inhibit FcΔRI-mediated mast cell degranulation but, surprisingly, without affecting aggregation-dependent tyrosine phosphorylation, calcium mobilization, or leukotriene synthesis. Furthermore, CD81 antibodies also inhibit mast cell degranulation in vivo as measured by reduced passive cutaneous anaphylaxis responses. These results reveal an unsuspected calcium-independent pathway of antigen receptor regulation, which is accessible to engagement by membrane proteins and on which novel therapeutic approaches to allergic diseases could be based
Rearrangement and Expression of Immunoglobulin Light Chain Genes Can Precede Heavy Chain Expression during Normal B Cell Development in Mice
In mouse mutants incapable of expressing ÎŒ chains, VÎșJÎș joints are detected in the CD43+ B cell progenitors. In agreement with these earlier results, we show by a molecular single cell analysis that 4â7% of CD43+ B cell progenitors in wild-type mice rearrange immunoglobulin (Ig)Îș genes before the assembly of a productive VHDHJH joint. Thus, ÎŒ chain expression is not a prerequisite to IgÎș light chain gene rearrangements in normal development. Overall, âŒ15% of the total CD43+ B cell progenitor population carry IgÎș gene rearrangements in wild-type mice. Together with the results obtained in the mouse mutants, these data fit a model in which CD43+ progenitors rearrange IgH and IgÎș loci independently, with a seven times higher frequency in the former. In addition, we show that in B cell progenitors VÎșJÎș joining rapidly initiates Îș chain expression, irrespective of the presence of a ÎŒ chain
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