The Pseudo-immunoreceptor Tyrosine-based Activation Motif of CD5 Mediates Its Inhibitory Action on B-cell Receptor Signaling

Gary-Gouy, Hélène; Bruhns, Pierre; Schmitt, C.; Dalloul, Ali; Daëron, Marc; Bismuth, Georges

doi:10.1074/jbc.275.1.548

Cited by 62 publications

(74 citation statements)

References 79 publications

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“…Lyn was constitutively associated with the BCR, while, in response to CD5 crosslinking, Syk was recruited, and SHP-1 uncoupled from CD5. This is consistent with the dissociation of SHP-1 in CD5-negative B cells, following activation, 23 Furthermore, our studies on LRs showed that CD5, CD79a and Syk, but not SHP-1, cohabit in the LRs after CD5 activation. Indeed, for tonsil and group II B-CLL B cells, CD5, seen initially outside the LRs, moved there, along with CD79 and sIgM, while SHP-1 was left behind.…”

Section: Discussionsupporting

confidence: 74%

Role of B-cell antigen receptor-associated molecules and lipid rafts in CD5-induced apoptosis of B CLL cells

Renaudineau¹,

Nédellec²,

Berthou³

et al. 2004

Leukemia

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A total of 40 patients with B-CLL were investigated for CD5-triggered apoptosis and categorized as 20 resistant (group I) and 20 sensitive patients (group II). The densities of surface IgM (sIgM) and CD5 were lower in group I than group II, as were the percentages of CD79b þ , CD38 þ , and Zap70-expressing B cells. CD5 signaling was mediated through the BCR in group II B cells, as established by coimmunoprecipitation of CD5 and CD79a and tyrosine phosphorylation of CD79a. Following colocalization of CD5 and sIgM in membrane lipid rafts (LRs), Syk became associated with these molecules, whereas SHP-1 was uncoupled from CD5. Nonresponsiveness to CD5 crosslinking in group I was ascribed to three possible abnormalities, and defined as three subgroups of patients. In subgroups Ia and Ib, CD5 and sIgM colocalized within the LRs. SHP-1 remained attached to the BCR in subgroup Ia, but not in subgroup Ib, where signal transduction was associated with an excess of truncated CD79b. In subgroup Ic, CD5 and sIgM segregated into different LRs, resulting in no signaling of apoptosis.

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Section: Discussionsupporting

confidence: 74%

Role of B-cell antigen receptor-associated molecules and lipid rafts in CD5-induced apoptosis of B CLL cells

Renaudineau¹,

Nédellec²,

Berthou³

et al. 2004

Leukemia

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“…15,16 In humans, CD5 induces an anergic state in lymphocytes and contributes to B-cell survival and interleukin-10 production, and CD5 expression on B-cells may serve as a marker of antigen exposure. 15,16 Assessment of CD5 expression by flow cytometry or immunohistochemistry has been widely used in the clinical work-up of B-cell lymphomas. CD5 expression is usually seen in chronic lymphocytic leukemia/small lymphocytic lymphoma or mantle cell lymphoma.…”

Section: Discussionmentioning

confidence: 99%

CD5-positive follicular lymphoma: clinicopathologic correlations and outcome in 88 cases

Liu

Zuo

et al. 2015

Modern Pathology

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Follicular lymphoma is a low-grade B-cell lymphoma of germinal center B-cell origin that typically lacks CD5 expression. We describe the clinicopathologic features of 88 cases of CD5+ follicular lymphoma (53 men, 35 women; median age, 60 years; range, 31-86). Follicular lymphoma was diagnosed initially in lymph nodes in 66 and extranodal sites in 22 patients. Eighty-one patients had lymphadenopathy, 66 had more than one involved site, 46 had bone marrow involvement, and 7 had splenomegaly. Staging information was available for 84 patients: 52 stage IV, 18 stage III, 12 stage II, and 2 stage I. Sixty-one cases were grade 1 or 2 and 27 were grade 3. The median proliferation index (Ki-67) was 30%. CD5 expression was detected by flow cytometry in 69, immunohistochemistry in 8, and both methods in 11 cases. The presence of t(14;18)(q32;q21)/IGH-BCL2 or other BCL2 translocation was detected in 28/44 (64%) cases. A total of 38 (43%) patients also had diffuse large B-cell lymphoma, concurrent with (n = 20), subsequent to (n = 13), or developing before CD5+ follicular lymphoma (n = 5). All patients received chemotherapy; 12 also received stem-cell transplantation. With a median follow-up of 55 months (range, 0.5-207), 15 patients died, 46 were alive with disease, and 20 were in clinical remission. Compared with a matched group of patients with CD5− follicular lymphoma, patients with CD5+ follicular lymphoma more commonly had an International Prognostic Index 42 (35/80 vs 10/99, Po0.001), more often developed diffuse large B-cell lymphoma (38/88 vs 17/99; Po 0.001), and had a shorter median progression-free survival (44 vs 89 months, P = 0.0042). Higher Ki-67 and International Prognostic Index were identified as poor prognostic factors in both the groups. We conclude that CD5 expression in follicular lymphoma is associated with a higher International Prognostic Index, higher rate of transformation to diffuse large B-cell lymphoma, and shorter progression-free survival.

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“…5 CD5 is a cell-surface receptor that has inhibitory effects on BCR signaling. 22 In this regard, CD5 could act to keep the fraction of autoreactive transitional B cells under control. The reduced expression of membrane CD19 increases the threshold for BCR stimulation.…”

Section: Discussionmentioning

confidence: 99%

B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele

et al. 2010

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Homozygous CD19 mutations lead to an antibody deficiency due to disruption of the CD19 complex and consequent impaired signaling by the B-cell antigen receptor. We studied the effects of heterozygous CD19 mutations on peripheral B-cell development and antibody responses in a large family with multiple consanguineous marriages. Sequence analysis of 96 family members revealed 30 carriers of the CD19 mutation. Lymphocyte subset counts were not significantly different between carriers and noncarriers in three different age groups (0-10 years; 11-18 years; adults). B cells of carriers had reduced CD19 and CD21 median expression levels, and had reduced proportions of transitional (0-10 years) and CD5 þ B cells (adults). CD19 carriers did not show clinical signs of immunodeficiency; they were well capable to produce normal serum Ig levels and had normal responses to primary and booster vaccinations. The frequency of mutated Vk alleles was not affected. Heterozygous loss of CD19 causes some changes in the naive B-cell compartment, but overall in vivo B-cell maturation or humoral immunity is not affected. Many antibody deficiencies are not monogenetic, but likely caused by a combination of multiple genetic variations. Therefore, functional analyses of immune cell function should be carried out to show whether heterozygous mutations contribute to disease.

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The Pseudo-immunoreceptor Tyrosine-based Activation Motif of CD5 Mediates Its Inhibitory Action on B-cell Receptor Signaling

Cited by 62 publications

References 79 publications

Role of B-cell antigen receptor-associated molecules and lipid rafts in CD5-induced apoptosis of B CLL cells

Role of B-cell antigen receptor-associated molecules and lipid rafts in CD5-induced apoptosis of B CLL cells

CD5-positive follicular lymphoma: clinicopathologic correlations and outcome in 88 cases

B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele

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