Co-receptors of B lymphocytes

O'Rourke, Lorraine M; Tooze, Reuben; Fearon, Douglas T.

doi:10.1016/s0952-7915(97)80077-5

Cited by 72 publications

(45 citation statements)

References 64 publications

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“…Since Lyn is apparently involved in activating BCR signal by phosphorylating ITAMs in Iga/Igb and Syk (DeFranco, 1997; Kurosaki, 1997;Pleiman et al, 1994;Reth and Wienands, 1997), our results support the contention that Lyn has both positive and negative roles in B cell activation (DeFranco, 1997; Kurosaki, 1997). The negative role of Lyn appears to be mediated in part by PIR-B as well as FcgRIIB and CD22 (Chan et al, 1997;Nishizumi et al, 1998;O'Rourke et al, 1997;Wang et al, 1996). Slight PIR-B tyrosine phosphorylation by BCR alone, although less ecient than occurring after coligation of BCR and PIR-B (Figure 2), might provide insights into the mechanism by which PIR-B modulates B cell activation in vivo.…”

Section: Discussionmentioning

confidence: 99%

Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1

et al. 1999

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Coligation of paired immunoglobulin-like receptor B (PIR-B) with B cell antigen receptor (BCR) blocks antigen-induced B cell activation. This inhibition is mediated in part by recruitment of SHP-1 and SHP-2 to the phosphorylated ITIMs in the cytoplasmic domain of PIR-B; however the molecular target(s) of these phosphatases remain elusive. Here we show that PIR-B ligation inhibits the BCR-induced tyrosine phosphorylation of Iga/Igb, Syk, Btk and phospholipase C (PLC)-g2. Overexpression of a catalytically inactive form of SHP-1 prevents the PIR-B-mediated inhibition of tyrosine phosphorylation of Syk, Btk, and PLC-g2. Dephosphorylation of Syk and Btk mediated by SHP-1 leads to a decrease of their kinase activity, which in turn inhibits tyrosine phosphorylation of PLC-g2. Furthermore, we de®ne a requirement for Lyn in mediating tyrosine phosphorylation of PIR-B. Based on these results, we propose a model of PIR-B-mediated inhibitory signaling in which coligation of PIR-B and BCR results in phosphorylation of ITIMs by Lyn, subsequent recruitment of SHP-1, and a resulting inhibition of the BCR-induced inositol 1,4,5-trisphosphate generation by dephosphorylation of Syk and Btk.

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Section: Discussionmentioning

confidence: 99%

Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1

et al. 1999

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“…Fc␥RII modulates BCR signaling only when it interacts with the antigen-IgG complex and is involved in negative feedback regulation of IgG production. In contrast, both CD22 and CD72 appear to interact constitutively with BCR and regulate negatively both mitogen-activated protein kinase activation and Ca 2ϩ mobilization induced by BCR ligation (12,13,(15)(16)(17). By negatively regulating BCR signaling whenever BCR is ligated, both of these co-receptors are implicated in setting a signaling threshold for BCR ligation.…”

Section: Cross-linking Of the B Cell Antigen Receptor (Bcr)mentioning

confidence: 99%

SHP-1 Requires Inhibitory Co-receptors to Down-modulate B Cell Antigen Receptor-mediated Phosphorylation of Cellular Substrates

Adachi¹,

Wienands²,

Wakabayashi³

et al. 2001

Journal of Biological Chemistry

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Signaling through the B cell antigen receptor (BCR) is negatively regulated by the SH2 domain-containing protein-tyrosine phosphatase SHP-1, which requires association with tyrosine-phosphorylated proteins for activation. Upon BCR ligation, SHP-1 has been shown to associate with the BCR, the cytoplasmic protein-tyrosine kinases Lyn and Syk, and the inhibitory co-receptors CD22 and CD72. How SHP-1 is activated by BCR ligation and regulates BCR signaling is, however, not fully understood. Here we demonstrate that, in the BCRexpressing myeloma line J558Lm3, CD72 expression reduces the BCR ligation-induced phosphorylation of the BCR component Ig␣/Ig␤ and its cytoplasmic effectors Syk and SLP-65. Substrate phosphorylation was restored by expression of dominant negative mutants of SHP-1, whereas the SHP-1 mutants failed to enhance phosphorylation of the cellular substrates in the absence of CD72. This indicates that SHP-1 is efficiently activated by CD72 but not by other pathways in J558Lm3 cells and that inhibition of SHP-1 specifically activated by CD72 reverses CD72-induced dephosphorylation of cellular substrates in these cells. Taken together, BCR-induced SHP-1 activation is likely to require inhibitory co-receptors such as CD72, and SHP-1 appears to mediate the negative regulatory effect of CD72 on BCR signaling by dephosphorylating Ig␣/Ig␤ and its downstream signaling molecules Syk and SLP-65. Cross-linking of the B cell antigen receptor (BCR)1 activates protein-tyrosine kinases (PTKs) and induces phosphorylation of the immunoreceptor tyrosine-based activation motifs in the cytoplasmic tails of the Ig␣/Ig␤ heterodimer, the signaling component of the BCR (1, 2 (2,3,5,8,9). The downstream signaling events appear to lead ultimately to proliferation, functional inactivation, or death of B cells. BCR signaling is regulated either positively by co-receptors such as CD19 and negatively by other co-receptors such as CD22 and the low affinity receptor for IgG (Fc␥RII) (10 -14). Fc␥RII modulates BCR signaling only when it interacts with the antigen-IgG complex and is involved in negative feedback regulation of IgG production. In contrast, both CD22 and CD72 appear to interact constitutively with BCR and regulate negatively both mitogen-activated protein kinase activation and Ca 2ϩ mobilization induced by BCR ligation (12,13,(15)(16)(17). By negatively regulating BCR signaling whenever BCR is ligated, both of these co-receptors are implicated in setting a signaling threshold for BCR ligation.The Src homology 2 (SH2) domain-containing protein-tyrosine phosphatase SHP-1 is involved in negative regulation of several receptors (18). For SHP-1 activation, its tandem SH2 domains need to be associated with a tyrosine-phosphorylated peptide (19). In B cells, CD22 has been shown to activate SHP-1. CD22 contains the conserved immunoreceptor tyrosinebased inhibition motifs (ITIMs) in the cytoplasmic regions (20). Upon tyrosine phosphorylation, the ITIMs of CD22 associate with and activate SHP-1. PIR-B and CD72 also contain ITIMs in...

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“…Although CD22 constitutively associates with BCR, coligation of CD22 with BCR further reduces BCR signaling such as MAPK activation (21), probably because the coligation enhances association between CD22 and BCR. It is suggested that by down-modulating BCR signaling constitutively, CD22 sets a threshold for BCR ligation (22)(23)(24). Such a threshold may play a role in protecting B cells from BCR firing either spontaneously or by weak cross-reactive interaction with Ags.…”

Section: Igation Of the Ag Receptor Of B Cells (Bcr)mentioning

confidence: 99%

CD72 Negatively Regulates Signaling Through the Antigen Receptor of B Cells

Adachi

Wakabayashi

Nakayama

et al. 2000

The Journal of Immunology

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The immunoreceptor tyrosine-based inhibition motif (ITIM) is found in various membrane molecules such as CD22 and the low-affinity Fc receptor for IgG in B cells and the killer cell-inhibitory receptor and Ly-49 in NK cells. Upon tyrosine phosphorylation at the ITIMs, these molecules recruit SH2 domain-containing phosphatases such as SH2-containing tyrosine phosphatase-1 and negatively regulate cell activity. The B cell surface molecule CD72 carries an ITIM and an ITIM-like sequence. We have previously shown that CD72 is phosphorylated and recruits SH2-containing tyrosine phosphatase-1 upon cross-linking of the Ag receptor of B cells (BCR). However, whether CD72 modulates BCR signaling has not yet been elucidated. In this paper we demonstrate that expression of CD72 down-modulates both extracellular signal-related kinase (ERK) activation and Ca2+ mobilization induced by BCR ligation in the mouse B lymphoma line K46μmλ, whereas BCR-mediated ERK activation was not reduced by the ITIM-mutated form of CD72. Moreover, coligation with CD72 with BCR reduces BCR-mediated ERK activation in spleen B cells of normal mice. These results indicate that CD72 negatively regulates BCR signaling. CD72 may play a regulatory role in B cell activation, probably by setting a threshold for BCR signaling.

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Co-receptors of B lymphocytes

Cited by 72 publications

References 64 publications

Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1

Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1

SHP-1 Requires Inhibitory Co-receptors to Down-modulate B Cell Antigen Receptor-mediated Phosphorylation of Cellular Substrates

CD72 Negatively Regulates Signaling Through the Antigen Receptor of B Cells

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