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1. Semaphorin 4C: A Novel Component of B-Cell Polarization in Th2 Driven Immune Responses

Author

Di Xue, Marylin Desjardins, Gabriel Nathan Kaufman, Marianne Beland, Salem Al-Tamemi, Eisha Ahmed, Shao Tao, Roland Friedel, Walid Mourad, and Bruce David Mazer

Subjects
B cell development, immune synapse, polarization, B cell differentiation, Murine models, Th2 responses, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Semaphorins are important molecules in embryonic development and multiple semaphorins have been identified as having key roles in immune regulation. To date, there is little known about Semaphorin 4C (Sema4C) in immune biology. We report for the first time that Sema4C is inducible in human and murine B-cells and may be important for normal B-cell development. Methods: Human Tonsillar B-cells were studied following activation via anti-CD40 antibodies in the presence or absence of representative Th1, Th2, and regulatory cytokines. Murine B-cells from WT and Sema4C-/- mice were similarly stimulated. B-cell phenotyping in WT and Sema4C mutant mice was performed by flow cytometry and lymphoid architecture was studied by immunohistochemistry. Sema4C expression and synapse formation was analyzed by confocal microscopy. Results: Gene Array studies performed on human tonsillar B-cells stimulated to produce IgE revealed that Sema4C was among the top genes expressed at 24 hours, and the only semaphorin to be increased under Th2 conditions. Validation studies demonstrated that human and murine B-cells expressed Sema4C under similar conditions. Sema4C-/- mice had impaired maturation of B-cell follicles in spleens and associated decreases in follicular and marginal zone B-cells as well as impaired IgG and IgA production. In keeping with a potential role in maturation of B-cells, Sema4C was expressed predominantly on CD27+ Human B-cells. Within 72 hours of B-cell activation, Sema4C was localized to one pole in a synapse-like structure, in association with F-Actin, BCR, and Plexin-B2. Cell polarization was impaired in Sema4C-/- mice. Conclusion: We have identified a novel immune semaphorin induced in human and murine B-cells under Th2 conditions. Sema4C appears to be a marker for human memory B-cells. It may be important for B-cell polarization and for the formation of normal splenic follicles.

Published
2016
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2. Corrigendum: Semaphorin 4C: A Novel Component of B-Cell Polarization in Th2-Driven Immune Responses

Author

Di Xue, Roland H. Friedel, Marianne Beland, Eisha Ahmed, Gabriel N. Kaufman, Walid Mourad, Marylin Desjardins, Salem Al-Tamemi, Shao Tao, and Bruce Mazer

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, semaphorin 4C, Immunology, B-cells, Murine models, Th2 responses, Immunological synapse, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Immune system, Semaphorin, B cell development, medicine, Immunology and Allergy, B cell differentiation, Original Research, polarization, biology, medicine.diagnostic_test, immune synapse, breakpoint cluster region, Correction, Marginal zone, Cell biology, 030104 developmental biology, biology.protein, Immunohistochemistry, Antibody, lcsh:RC581-607, 030215 immunology
Abstract

Background Semaphorins are important molecules in embryonic development and multiple semaphorins have been identified as having key roles in immune regulation. To date, there is little known about Semaphorin 4C (Sema4C) in immune biology. We report for the first time that Sema4C is inducible in human and murine B-cells and may be important for normal B-cell development. Methods Human tonsillar B-cells were studied following activation via anti-CD40 antibodies in the presence or absence of representative Th1, Th2, and regulatory cytokines. Murine B-cells from WT and Sema4C−/− mice were similarly stimulated. B-cell phenotyping in WT and Sema4C mutant mice was performed by flow cytometry and lymphoid architecture was studied by immunohistochemistry. Sema4C expression and synapse formation were analyzed by confocal microscopy. Results Gene array studies performed on human tonsillar B-cells stimulated to produce IgE revealed that Sema4C was among the top genes expressed at 24 h, and the only semaphorin to be increased under Th2 conditions. Validation studies demonstrated that human and murine B-cells expressed Sema4C under similar conditions. Sema4C−/− mice had impaired maturation of B-cell follicles in spleens and associated decreases in follicular and marginal zone B-cells as well as impaired IgG and IgA production. In keeping with a potential role in maturation of B-cells, Sema4C was expressed predominantly on CD27+ human B-cells. Within 72 h of B-cell activation, Sema4C was localized to one pole in a synapse-like structure, in association with F-actin, B-cell receptor, and Plexin-B2. Cell polarization was impaired in Sema4C−/− mice. Conclusion We have identified a novel immune semaphorin induced in human and murine B-cells under Th2 conditions. Sema4C appears to be a marker for human memory B-cells. It may be important for B-cell polarization and for the formation of normal splenic follicles.

Published
2016
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3. Canadian Society of Allergy and Clinical Immunology annual scientific meeting 2016

Author

Mohammad A. Alsayegh, Hanan Alshamali, Mousa Khadada, Amanda Ciccolini, Anne K. Ellis, Diana Quint, William Powley, Laurie Lee, Yahya Fiteih, Shairaz Baksh, Harissios Vliagoftis, Sebastien K. Gerega, Brad Millson, Katia Charland, Stephane Barakat, Xichun Sun, Ricardo Jimenez, Susan Waserman, Mark J. FitzGerald, Jacques Hébert, Josiane Cognet-Sicé, Kevin E. Renahan, Saiful Huq, Rishma Chooniedass, Scott Sawyer, Hans Pasterkamp, Allan Becker, Steven G. Smith, Shiyuan Zhang, Kavisha Jayasundara, Claire Tacon, Alex Simidchiev, Gilbert Nadeau, Necdet Gunsoy, Hana Mullerova, Frank Albers, Young Woong Kim, Casey P. Shannon, Amrit Singh, Helen Neighbour, Mark Larché, Scott J. Tebbutt, Annika Klopp, Lorena Vehling, Allan B. Becker, Padmaja Subbarao, Piushkumar J. Mandhane, Stuart E. Turvey, Malcolm R. Sears, Meghan B. Azad, and the Canadian Healthy Infant Longitudinal Development Study Investigators, Keely Loewen, Barret Monchka, Salaheddin M. Mahmud, Geert ‘t Jong, Cristina Longo, Gillian Bartlett, Francine M. Ducharme, Tibor Schuster, Brenda MacGibbon, Tracie Barnett, Michelle L. North, Jeff Brook, Elizabeth Lee, Vanessa Omana, Jenny Thiele, Lisa M. Steacy, Greg Evans, Miriam Diamond, Gordon L. Sussman, Yann Amistani, Kathy Abiteboul, Mark W. Tenn, ChenXi Yang, Christopher Carlsten, Edward M. Conway, Douglas Mack, Yasmin Othman, Colin M. Barber, Chrystyna Kalicinsky, Andrea E. Burke, Mary Messieh, Parameswaran Nair, Chun T. Che, Lindsay Douglas, Joel Liem, Lucy Duan, Charlotte Miller, Pascale Dupuis, Lori A. Connors, Michael N. Fein, Joseph Shuster, Hani Hadi, Brooke Polk, Nikita Raje, Roxane Labrosse, Philippe Bégin, Louis Paradis, Anne Des Roches, Jonathan Lacombe-Barrios, Sanju Mishra, Gina Lacuesta, Meredith Chiasson, Babar Haroon, Kara Robertson, Thomas Issekutz, Desmond Leddin, Stephen Couban, Lori Connors, Adrienne Roos, Amin Kanani, Edmond S. Chan, Robert Schellenberg, Lana Rosenfield, Anna Cvetkovic, Kevin Woodward, Jaclyn Quirt, Wade T. A. Watson, Edson Castilho, Jennifer A. Sullivan, Beverley Temple, Donna Martin, Victoria E. Cook, Christopher Mills, Elodie Portales-Casamar, Lisa W. Fu, Alexander Ho, Jeffrey Zaltzman, Lucy Chen, Peter Vadas, Sofianne Gabrielli, Ann Clarke, Harley Eisman, Judy Morris, Lawrence Joseph, Sebastien LaVieille, Moshe Ben-Shoshan, François Graham, Charles Barnes, Jay Portnoy, Vincent Stagg, Elinor Simons, Diana Lefebvre, David Dai, Piushkumar Mandhane, Malcolm Sears, Herman Tam, F. Estelle R. Simons, Dhaifallah Alotaibi, Bassel Dawod, Matthew C. Tunis, Jean Marshall, Marylin Desjardins, Marianne Béland, Duncan Lejtenyi, Jean-Phillipe Drolet, Martine Lemire, Christos Tsoukas, Francisco J.D. Noya, Reza Alizadehfar, Christine T. McCusker, Bruce D. Mazer, Danay Maestre-Batlle, Evelyn Gunawan, Christopher F. Rider, Anette K. Bølling, Olga M. Pena, Daniel Suez, Isaac Melamed, Iftikhar Hussain, Mark Stein, Sudhir Gupta, Kenneth Paris, Sandor Fritsch, Christelle Bourgeois, Heinz Leibl, Barbara McCoy, Martin Noel, Leman Yel, Ori Scott, Brenda Reid, Adelle Atkinson, Vy Hong-Diep Kim, Chaim M. Roifman, Eyal Grunebaum, Eiman AlSelahi, Fernando Aleman, Amber Oberle, Mike Trus, Gordon Sussman, Amin S. Kanani, Olivier Chambenoi, Sima Chiva-Razavi, Savannah Grodecki, Nikhil Joshi, Peter Menikefs, David Holt, Teresa Pun, Damian Tworek, Raphael Hanna, Delia Heroux, Elli Rosenberg, Leah Stiemsma, Stuart Turvey, Judah Denburg, Christopher Mill, Timothy Teoh, Preeti Zimmer, Vishal Avinashi, Mihaela Paina, Ahmed A. Darwish Hassan, John Paul Oliveria, Chris Olesovsky, Gail Gauvreau, Linda Pedder, Paul K. Keith, Greg Plunkett, Michelle Bolner, Persia Pourshahnazari, Donald Stark, Kateryna Vostretsova, Andrew Moses, Andrew Wakeman, Alexander Singer, Thomas Gerstner, Elissa Abrams, Sara F. Johnson, and Roberta L. Woodgate

Subjects
Asthma, Food Allergy, Allergic Rhinitis, Chronic Granulomatous Disease, Immunologic diseases. Allergy, RC581-607
Published
2017
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