Syk Tyrosine Kinase Is Required for the Positive Selection of Immature B Cells into the Recirculating B Cell Pool

doi:10.1084/jem.186.12.2013

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J. Exp. Med., Volume 186, Number 12, December 15, 1997 2013-2021

Syk Tyrosine Kinase Is Required for the Positive Selection of Immature B Cells into the Recirculating B Cell Pool

By Martin Turner,^* Adam Gulbranson-Judge, Marian E. Quinn,^* Alice E. Walters,^* Ian C.M. MacLennan, and Victor L.J. Tybulewicz^*

From the ^* National Institute for Medical Research, Mill Hill, London, NW7 1AA, United Kingdom; and the Department of Immunology, University of Birmingham Medical School, Birmingham, B15 2TT, United Kingdom

The tyrosine kinase Syk has been implicated as a key signal transducer from the B cell antigen receptor (BCR). We show herethat mutation of the Syk gene completely blocks the maturationof immature B cells into recirculating cells and stops their entryinto B cell follicles. Furthermore, using radiation chimeras wedemonstrate that this developmental block is due to the absenceof Syk in the B cells themselves. Syk-deficient B cells are shownto have the life span of normal immature B cells. If this is extendedby over-expression of Bcl-2, they accumulate in the T zone andred pulp of the spleen in increased numbers, but still fail tomature to become recirculating follicular B cells. Despite thisdefect in maturation, Syk-deficient B cells were seen to giverise to switched as well as nonswitched splenic plasma cells.Normally only a proportion of immature B cells is recruited intothe recirculating pool. Our results suggest that Syk transducesa BCR signal that is absolutely required for the positive selectionof immature B cells into the recirculating B cell pool.

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Tian, Q., Beardall, M., Xu, Y., Li, J., Parker, D. C., Casanova, N., Bakke, A. C., Chen, C. (2006). B Cells Expressing a Natural Polyreactive Autoantibody Have a Distinct Phenotype and Are Overrepresented in Immunoglobulin Heavy Chain Transgenic Mice. J. Immunol. 177: 2412-2422 [Abstract] [Full Text]
Craxton, A., Draves, K. E., Gruppi, A., Clark, E. A. (2005). BAFF regulates B cell survival by downregulating the BH3-only family member Bim via the ERK pathway. J. Exp. Med. 202: 1363-1374 [Abstract] [Full Text]
Vigorito, E., Gambardella, L., Colucci, F., McAdam, S., Turner, M. (2005). Vav proteins regulate peripheral B-cell survival. Blood 106: 2391-2398 [Abstract] [Full Text]
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Danzer, C.-P., Collins, B. E., Blixt, O., Paulson, J. C., Nitschke, L. (2003). Transitional and marginal zone B cells have a high proportion of unmasked CD22: implications for BCR signaling. Int Immunol 15: 1137-1147 [Abstract] [Full Text]
Jankovic, M., Nussenzweig, M. C. (2003). OcaB regulates transitional B cell selection. Int Immunol 15: 1099-1104 [Abstract] [Full Text]
Yokozeki, T., Adler, K., Lankar, D., Bonnerot, C. (2003). B Cell Receptor-Mediated Syk-Independent Activation of Phosphatidylinositol 3-Kinase, Ras, and Mitogen-Activated Protein Kinase Pathways. J. Immunol. 171: 1328-1335 [Abstract] [Full Text]
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Julien, S., Soulas, P., Garaud, J.-C., Martin, T., Pasquali, J.-L. (2002). B Cell Positive Selection by Soluble Self-Antigen. J. Immunol. 169: 4198-4204 [Abstract] [Full Text]
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HASLER, P., ZOUALI, M. (2001). B cell receptor signaling and autoimmunity. FASEB J. 15: 2085-2098 [Abstract] [Full Text]
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Dillon, S. R., Constantinescu, A., Schlissel, M. S. (2001). Annexin V Binds to Positively Selected B Cells. J. Immunol. 166: 58-71 [Abstract] [Full Text]
Sanchez, P., Crain-Denoyelle, A.-M., Daras, P., Gendron, M.-C., Kanellopoulos-Langevin, C. (2000). The level of expression of {micro} heavy chain modifies the composition of peripheral B cell subpopulations. Int Immunol 12: 1459-1466 [Abstract] [Full Text]
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Chumley, M. J., Dal Porto, J. M., Kawaguchi, S., Cambier, J. C., Nemazee, D., Hardy2, R. R. (2000). A VH11V{kappa}9 B Cell Antigen Receptor Drives Generation of CD5+ B Cells Both In Vivo and In Vitro. J. Immunol. 164: 4586-4593 [Abstract] [Full Text]
Pappu, R., Cheng, A. M., Li, B., Gong, Q., Chiu, C., Griffin, N., White, M., Sleckman, B. P., Chan, A. C. (1999). Requirement for B Cell Linker Protein (BLNK) in B Cell Development. Science 286: 1949-1954 [Abstract] [Full Text]
Colucci, F., Turner, M., Schweighoffer, E., Guy-Grand, D., Di Bartolo, V., Salcedo, M., Tybulewicz, V. L. J., Di Santo, J. P. (1999). Redundant Role of the Syk Protein Tyrosine Kinase in Mouse NK Cell Differentiation. J. Immunol. 163: 1769-1774 [Abstract] [Full Text]
Loder, F., Mutschler, B., Ray, R. J., Paige, C. J., Sideras, P., Torres, R., Lamers, M. C., Carsetti, R. (1999). B Cell Development in the Spleen Takes Place in Discrete Steps and Is Determined by the Quality of B Cell Receptor�derived Signals. J. Exp. Med. 190: 75-90 [Abstract] [Full Text]
Maas, A., Dingjan, G. M., Grosveld, F., Hendriks, R. W. (1999). Early Arrest in B Cell Development in Transgenic Mice That Express the E41K Bruton's Tyrosine Kinase Mutant Under the Control of the CD19 Promoter Region. J. Immunol. 162: 6526-6533 [Abstract] [Full Text]
Cariappa, A., Kim, T. J., Pillai, S. (1999). Accelerated Emigration of B Lymphocytes in the Xid Mouse. J. Immunol. 162: 4417-4423 [Abstract] [Full Text]
Kiefer, F., Brumell, J., Al-Alawi, N., Latour, S., Cheng, A., Veillette, A., Grinstein, S., Pawson, T. (1998). The Syk Protein Tyrosine Kinase Is Essential for Fcgamma Receptor Signaling in Macrophages and Neutrophils. Mol. Cell. Biol. 18: 4209-4220 [Abstract] [Full Text]
Martin, F., Won, W.-J., Kearney, J. F. (1998). Generation of the Germline Peripheral B Cell Repertoire: VH81X-{lambda} B Cells Are Unable to Complete All Developmental Programs. J. Immunol. 160: 3748-3758 [Abstract] [Full Text]
Schmidt, K. N., Hsu, C. W., Griffin, C. T., Goodnow, C. C., Cyster, J. G. (1998). Spontaneous Follicular Exclusion of SHP1-deficient B Cells Is Conditional on the Presence of Competitor Wild-type B Cells. J. Exp. Med. 187: 929-937 [Abstract] [Full Text]
Ganju, R. K., Brubaker, S. A., Chernock, R. D., Avraham, S., Groopman, J. E. (2000). beta -Chemokine Receptor CCR5 Signals through SHP1, SHP2, and Syk. J. Biol. Chem. 275: 17263-17268 [Abstract] [Full Text]
Zhang, J., Billingsley, M. L., Kincaid, R. L., Siraganian, R. P. (2000). Phosphorylation of Syk Activation Loop Tyrosines Is Essential for Syk Function. AN IN VIVO STUDY USING A SPECIFIC ANTI-Syk ACTIVATION LOOP PHOSPHOTYROSINE ANTIBODY. J. Biol. Chem. 275: 35442-35447 [Abstract] [Full Text]
Levine, M. H., Haberman, A. M., Sant'Angelo, D. B., Hannum, L. G., Cancro, M. P., Janeway, C. A. Jr., Shlomchik, M. J. (2000). A B-cell receptor-specific selection step governs immature to mature B cell differentiation. Proc. Natl. Acad. Sci. USA 97: 2743-2748 [Abstract] [Full Text]