<?xml version="1.0" encoding="UTF-8"?><xmi:XMI xmlns:pos="http:///org/u_compare/shared/label/penn/pos.ecore" xmlns:grammatical="http:///org/u_compare/shared/label/penn/function/grammatical.ecore" xmlns:general="http:///org/u_compare/shared/label/penn/pos/general.ecore" xmlns:cas="http:///uima/cas.ecore" xmlns:stanford="http:///org/u_compare/shared/label/stanford.ecore" xmlns:semantic2="http:///uk/ac/nactem/semantic.ecore" xmlns:bioie="http:///org/u_compare/shared/label/penn/pos/bioie.ecore" xmlns:function="http:///org/u_compare/shared/label/penn/function.ecore" xmlns:tcas="http:///uima/tcas.ecore" xmlns:bio="http:///org/u_compare/shared/semantic/bio.ecore" xmlns:syntactic="http:///org/u_compare/shared/syntactic.ecore" xmlns:comparable="http:///org/u_compare/shared/comparable.ecore" xmlns:examples="http:///org/apache/uima/examples.ecore" xmlns:label="http:///org/u_compare/shared/label.ecore" xmlns:xmi="http://www.omg.org/XMI" xmlns:general2="http:///org/u_compare/shared/label/penn/bracket/general.ecore" xmlns:shared="http:///org/u_compare/shared.ecore" xmlns:fragment="http:///org/u_compare/shared/document/fragment.ecore" xmlns:document="http:///org/u_compare/shared/document.ecore" xmlns:bracket="http:///org/u_compare/shared/label/penn/bracket.ecore" xmlns:text="http:///org/u_compare/shared/label/penn/function/text.ecore" xmlns:structure="http:///org/u_compare/shared/document/structure.ecore" xmlns:text2="http:///org/u_compare/shared/document/text.ecore" xmlns:release="http:///org/u_compare/shared/label/penn/pos/release.ecore" xmlns:semantic="http:///org/u_compare/shared/semantic.ecore" xmlns:nontext="http:///org/u_compare/shared/document/nontext.ecore" xmlns:conll="http:///org/u_compare/shared/label/conll.ecore" xmlns:chemical="http:///org/u_compare/shared/semantic/chemical.ecore" xmlns:semantic3="http:///org/u_compare/shared/label/penn/function/semantic.ecore" xmlns:release2="http:///org/u_compare/shared/label/penn/bracket/release.ecore" xmlns:coindex="http:///org/u_compare/shared/label/penn/coindex.ecore" xmi:version="2.0"><cas:NULL xmi:id="0"/><cas:Sofa xmi:id="1" sofaNum="1" sofaID="_InitialView" mimeType="text" sofaString="Skeletal muscle type ryanodine receptor is involved in calcium signaling in human B lymphocytes. &#10;The regulation of intracellular free Ca2+ concentration ([Ca2+]i) in B cells remains poorly understood and is presently explained almost solely by inositol 1,4,5-triphosphate (IP3)-mediated Ca2+ release, followed by activation of a store-operated channel mechanism. In fact, there are reports indicating that IP3 production does not always correlate with the magnitude of Ca2+ release. We demonstrate here that human B cells express a ryanodine receptor (RYR) that functions as a Ca2+ release channel during the B cell antigen receptor (BCR)-stimulated Ca2+ signaling process. Immunoblotting studies showed that both human primary CD19(+) B and DAKIKI cells express a 565-kDa immunoreactive protein that is indistinguishable in molecular size and immunoreactivity from the RYR. Selective reverse transcription-polymerase chain reaction, restriction fragment length polymorphism, and sequencing of cloned cDNA indicated that the major isoform of the RYR expressed in primary CD19(+) B and DAKIKI cells is identical to the skeletal muscle type (RYR1). Saturation analysis of [3H]ryanodine binding yielded Bmax = 150 fmol/mg of protein and Kd = 110 nM in DAKIKI cells. In fluo-3-loaded CD19(+) B and DAKIKI cells, 4-chloro-m-cresol, a potent activator of Ca2+ release mediated by the ryanodine-sensitive Ca2+ release channel, induced Ca2+ release in a dose-dependent and ryanodine-sensitive fashion. Furthermore, BCR-mediated Ca2+ release in CD19(+) B cells was significantly altered by 4-chloro-m-cresol and ryanodine. These results indicate that RYR1 functions as a Ca2+ release channel during BCR-stimulated Ca2+ signaling and suggest that complex Ca2+ signals that control the cellular activities of B cells may be generated by cooperation of the IP3 receptor and RYR1. 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