CD44-stimulated human B cells express transcripts specifically involved in immunomodulation and inflammation as analyzed by DNA microarrays

Högerkorp, Carl-Magnus; Bilke, Sven; Breslin, Thomas A.; Ingvarsson, Sigurður; Borrebaeck, Carl

doi:10.1182/blood-2002-06-1837

Cited by 25 publications

(13 citation statements)

References 59 publications

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“…During the germinal center reaction, however, CD44 is downregulated (Dahlenborg et al, 1997;Feuillard et al, 1995;Kremmidiotis and Zola, 1995). CD44 ligation by anti-CD44 in human B cells also results in upregulation of the genes for IL-6, IL-1a, and b 2 -adrenergic receptor (b 2 -AR)-indicating a role in immunomodulation and inflammation (Hogerkorp et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Mouse B Cell Activation is Inhibited by CD44 Cross-Linking

Wyant

Fisher

McKallip

et al. 2005

Immunological Investigations

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Lymphocyte activation and trafficking are indispensable to the immune system. CD44 is an adhesion molecule with known importance in T cell activation, lymphocyte trafficking, and tumor metastasis. Although CD44 has been shown to participate in the activation, rolling and adhesion, and homing of T cells, the role of CD44 on B cells is relatively unknown. The effects of CD44 cross-linking on murine B cell activation via CD40L was explored using the anti-CD44 mAbs RK3G9 and IM7. When immobilized on a plate, both RK3G9 and IM7 were found to strongly inhibit B cell proliferation and Ig production, especially at lower cell input concentrations. IgE inhibition was especially prominent. In contrast, soluble RK3G9 added to the B cell cultures had no effect. The inhibitory effect of anti-CD44 on B cell activation was not influenced by the addition of the anti-FcgammaRII, indicating that Fc cross-linking did not play a role in this inhibition. As Ig production requires several days for both B cell proliferation and differentiation to occur, the effects of delayed addition of immobilized anti-CD44 mAbs were studied, and the results indicated no inhibition after 96 hrs of culture. Finally, B cells were activated by either LPS or anti-IgM F(ab')2. While LPS-induced B cell activation was inhibited by immobilized anti-CD44 mAbs, anti-IgM activation was refractory. Interestingly, addition of both anti-IgM and CD40L or LPS resulted in some modulation of the inhibitory activity. These results suggest that CD44 cross-linking could control polyclonal B cell activation by CD40L, but allow sIgM/CD40L activation to continue.

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Section: Introductionmentioning

confidence: 99%

Mouse B Cell Activation is Inhibited by CD44 Cross-Linking

Wyant

Fisher

McKallip

et al. 2005

Immunological Investigations

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“…Lymphocyte homeostasis can control the balance between an insufficient number of cells to mount an immune response or the excessive proliferation and/or overstimulation of an immune response associated with pathological conditions, such as cancer and autoimmune disorders (16,42). Studies using antibodies to block CD44 function have demonstrated a role in lymphocyte activation, differentiation, homing/migration, and proliferation (15,21,31,44,47). We have shown that CD44 expression is diminished in the Ets1 ⌬VII mutants.…”

Section: Thymomegaly In Ets1mentioning

confidence: 99%

Thymomegaly, Microsplenia, and Defective Homeostatic Proliferation of Peripheral Lymphocytes in p51-Ets1 Isoform-Specific Null Mice

Higuchi

Bartel

Masuya³

et al. 2007

Molecular and Cellular Biology

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Ets1 is a member of the Ets transcription factor family. Alternative splicing of exon VII results in two naturally occurring protein isoforms: full-length Ets1 (p51-Ets1) and Ets1⌬VII (p42-Ets1). These isoforms bear key distinctions regarding protein-protein interactions, DNA binding kinetics, and transcriptional target specificity. Disruption of both Ets1 isoforms in mice results in the loss of detectable NK and NKT cell activity and defects in B and T lymphocytes. We generated mice that express only the Ets1 ⌬VII isoform. Ets1⌬VII homozygous mice express no p51-Ets1 and elevated levels of the p42-Ets1 protein relative to the wild type and display increased perinatal lethality, thymomegaly, and peripheral lymphopenia. Proliferation was increased in both the thymus and the spleen, while apoptosis was decreased in the thymus and increased in the spleen of homozygotes. Significant elevations of CD8 ؉ and CD8 ؉ CD4 ؉ thymocytes were observed. Lymphoid cell (CD19 ؉ , CD4 ؉ , and CD8 ؉ ) reductions were predominantly responsible for diminished spleen cellularity, with fewer memory cells and a failure of homeostatic proliferation to maintain peripheral lymphocytes. Collectively, the Ets1⌬VII mutants demonstrate lymphocyte maturation defects associated with misregulation of p16 Ink4a , p27Kip1 , and CD44. Thus, a balance in the differential regulation of Ets1 isoforms represents a potential mechanism in the control of lymphoid maturation and homeostasis.

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“…P2RY1 is a member of a family of G-protein-coupled receptors that are expressed on monocytes and macrophages and are involved in inflammatory and immunity pathways [20]. MLLT3 is known to regulate erythrocyte and megakaryocyte differentiation [21], and is also induced by ligation of CD44, a cell surface receptor for hyaluronan (HA) the concentration of which is increased in inflammatory and immune responses, and which also binds to LYVE-1 [22]. Mutation of the MLLT3 gene has also been linked to a patient with neuromotor development delay, cerebellar ataxia and epilepsy [23].…”

Section: Discussionmentioning

confidence: 99%