| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Immunology, Faculty of Medicine, Technion, and
Endocrine Research Unit, Carmel Medical Center, Haifa, Israel
Positive signaling is now thought to be important for B cell maturation, although the nature of such signals has not yet been defined. We are studying the regulatory role of B cell Ag receptor (BCR) signaling in mediating positive selection of immature B cells. To do so, we use Ig transgenic mice (3-83Tg) that are deficient in CD19, thus generating a monoclonal immature B cell population expressing signaling-incompetent BCR. Immature 3-83Tg CD19-/- B cells undergo developmental arrest in the bone marrow, allowing maturation only to cells that effectively compensate for the compromised receptor by elevated levels of BCR. We find that developmentally arrested 3-83Tg CD19-/- B cells fail to impose L chain allelic exclusion and undergo intensive V(D)J recombination to edit their BCR. Furthermore, immature 3-83Tg CD19-/- B cells, which were grown in vitro, failed to undergo positive selection and to survive when adoptively transferred into normal recipients. However, elevation of BCR expression levels, obtained by transgene homozygosity, effectively compensated for the compromised BCR and completely restored BCR-mediated Ca2+ influx, allelic exclusion, and positive selection. Our results suggest that the BCR signaling threshold mediates positive selection of developing B cells, and that a receptor-editing mechanism has an important role in rescuing cells that fail positive selection because of incompetent receptors.
This article has been cited by other articles:
|
|
 |
|
  B. R. Schram, L. E. Tze, L. B. Ramsey, J. Liu, L. Najera, A. L. Vegoe, R. R. Hardy, K. L. Hippen, M. A. Farrar, and T. W. Behrens B Cell Receptor Basal Signaling Regulates Antigen-Induced Ig Light Chain Rearrangements J. Immunol., April 1, 2008; 180(7): 4728 - 4741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, J. Feng, C.-F. Qi, Z. Li, H. C. Morse III, and S. H. Clarke Transitional B Cells Lose Their Ability to Receptor Edit but Retain Their Potential for Positive and Negative Selection J. Immunol., December 1, 2007; 179(11): 7544 - 7552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Lamoureux, L. C. Watson, M. Cherrier, P. Skog, D. Nemazee, and A. J. Feeney Reduced receptor editing in lupus-prone MRL/lpr mice J. Exp. Med., November 26, 2007; 204(12): 2853 - 2864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Edry, S. B. Koralov, K. Rajewsky, and D. Melamed Spontaneous Class Switch Recombination in B Cell Lymphopoiesis Generates Aberrant Switch Junctions and Is Increased after VDJ Rearrangement J. Immunol., November 15, 2007; 179(10): 6555 - 6560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Verkoczy, B. Duong, P. Skog, D. Ait-Azzouzene, K. Puri, J. L. Vela, and D. Nemazee Basal B Cell Receptor-Directed Phosphatidylinositol 3-Kinase Signaling Turns Off RAGs and Promotes B Cell-Positive Selection J. Immunol., May 15, 2007; 178(10): 6332 - 6341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Llorian, Z. Stamataki, S. Hill, M. Turner, and I.-L. Martensson Cutting Edge: The PI3K p110{delta} Is Required for Down-Regulation of RAG Expression in Immature B Cells J. Immunol., February 15, 2007; 178(4): 1981 - 1985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Melamed, O. Messika, L. Glass-Marmor, and A. Miller Modulation of matrix metalloproteinase-9 (MMP-9) secretion in B lymphopoiesis Int. Immunol., September 1, 2006; 18(9): 1355 - 1362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sirac, C. Carrion, S. Duchez, I. Comte, and M. Cogne Light chain inclusion permits terminal B cell differentiation and does not necessarily result in autoreactivity PNAS, May 16, 2006; 103(20): 7747 - 7752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Diamant, Z. Keren, and D. Melamed CD19 regulates positive selection and maturation in B lymphopoiesis: lack of CD19 imposes developmental arrest of immature B cells and consequential stimulation of receptor editing Blood, April 15, 2005; 105(8): 3247 - 3254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hayashi, T. Nojima, R. Goitsuka, and D. Kitamura Impaired Receptor Editing in the Primary B Cell Repertoire of BASH-Deficient Mice J. Immunol., November 15, 2004; 173(10): 5980 - 5988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Edry and D. Melamed Receptor Editing in Positive and Negative Selection of B Lymphopoiesis J. Immunol., October 1, 2004; 173(7): 4265 - 4271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Seagal, E. Edry, H. Naftali, and D. Melamed Generation and selection of an IgG-driven autoimmune repertoire during B-lymphopoiesis in Ig{micro}-deficient/lpr mice Int. Immunol., July 1, 2004; 16(7): 905 - 913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Keren, E. Diamant, O. Ostrovsky, E. Bengal, and D. Melamed Modification of Ligand-independent B Cell Receptor Tonic Signals Activates Receptor Editing in Immature B Lymphocytes J. Biol. Chem., April 2, 2004; 279(14): 13418 - 13424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Middendorp and R. W. Hendriks Cellular Maturation Defects in Bruton's Tyrosine Kinase-Deficient Immature B Cells Are Amplified by Premature B Cell Receptor Expression and Reduced by Receptor Editing J. Immunol., February 1, 2004; 172(3): 1371 - 1379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Otero and R. C. Rickert CD19 Function in Early and Late B Cell Development. II. CD19 Facilitates the Pro-B/Pre-B Transition J. Immunol., December 1, 2003; 171(11): 5921 - 5930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Seagal, E. Edry, Z. Keren, N. Leider, O. Benny, M. Machluf, and D. Melamed A Fail-safe Mechanism for Negative Selection of Isotype-switched B Cell Precursors Is Regulated by the Fas/FasL Pathway J. Exp. Med., November 17, 2003; 198(10): 1609 - 1619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shoham, R. Rajapaksa, C. Boucheix, E. Rubinstein, J. C. Poe, T. F. Tedder, and S. Levy The Tetraspanin CD81 Regulates the Expression of CD19 During B Cell Development in a Postendoplasmic Reticulum Compartment J. Immunol., October 15, 2003; 171(8): 4062 - 4072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Leider and D. Melamed Differential c-Myc Responsiveness to B Cell Receptor Ligation in B Cell-Negative Selection J. Immunol., September 1, 2003; 171(5): 2446 - 2452. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
