B-cell antigen receptor (BCR) signalling and its regulation through negative and positive regulators are critical for balancing B-cell response and function. Human Fc receptor like-2 (FCRL2), a member of the newly identified FCRL family, could influence B-cell signalling due to possession of both immunoreceptor tyrosine-based activation and inhibitory motifs (ITAM and ITIM). Since the natural ligand of FCRL2 has not been identified, we generated FCRL2-specific monoclonal antibodies (mAbs) and employed them to investigate the influence of FCRL2 stimulation on BCR signalling in an FCRL2-expressing B-cell line. Two anti-FCRL2 mAb-producing hybridoma clones (5A7-E7 and 3D8-G8) were selected. None of the mAbs displayed any cross-reactivity with the other members of the FCRL family including recombinant FCRL1, -3, -4 and -5, as tested by FACS and ELISA techniques. Engagement of the FCRL2 by these mAbs resulted in significant inhibition of BCR signalling mediators such as calcium mobilization and phosphorylation of the mitogen-activated protein kinases Erk, p38 and Jnk. These findings indicate that the FCRL2 ITIM motifs are functional and the anti-FCRL2 mAbs may mimic the natural ligand of FCRL2 by induction of inhibitory signals in B cells.

Shabani, M., Bayat, A.A., Jeddi-Tehrani, M., Rabbani, H., Hojjat-Farsangi, M., Ulivieri, C., et al. (2014). Ligation of human Fc receptor like-2 (FCRL2) by monoclonal antibodies downregulates B cell receptor mediated signaling. IMMUNOLOGY, 143(3), 341-353 [10.1111/imm.12311].

Ligation of human Fc receptor like-2 (FCRL2) by monoclonal antibodies downregulates B cell receptor mediated signaling

Ulivieri C.;Baldari C.;
2014-01-01

Abstract

B-cell antigen receptor (BCR) signalling and its regulation through negative and positive regulators are critical for balancing B-cell response and function. Human Fc receptor like-2 (FCRL2), a member of the newly identified FCRL family, could influence B-cell signalling due to possession of both immunoreceptor tyrosine-based activation and inhibitory motifs (ITAM and ITIM). Since the natural ligand of FCRL2 has not been identified, we generated FCRL2-specific monoclonal antibodies (mAbs) and employed them to investigate the influence of FCRL2 stimulation on BCR signalling in an FCRL2-expressing B-cell line. Two anti-FCRL2 mAb-producing hybridoma clones (5A7-E7 and 3D8-G8) were selected. None of the mAbs displayed any cross-reactivity with the other members of the FCRL family including recombinant FCRL1, -3, -4 and -5, as tested by FACS and ELISA techniques. Engagement of the FCRL2 by these mAbs resulted in significant inhibition of BCR signalling mediators such as calcium mobilization and phosphorylation of the mitogen-activated protein kinases Erk, p38 and Jnk. These findings indicate that the FCRL2 ITIM motifs are functional and the anti-FCRL2 mAbs may mimic the natural ligand of FCRL2 by induction of inhibitory signals in B cells.
2014
Shabani, M., Bayat, A.A., Jeddi-Tehrani, M., Rabbani, H., Hojjat-Farsangi, M., Ulivieri, C., et al. (2014). Ligation of human Fc receptor like-2 (FCRL2) by monoclonal antibodies downregulates B cell receptor mediated signaling. IMMUNOLOGY, 143(3), 341-353 [10.1111/imm.12311].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/47122
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