HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fuentes-Pananá, E. M. Articles by Monroe, J. G. Search for Related Content PubMed PubMed Citation Articles by Fuentes-Pananá, E. M. Articles by Monroe, J. G.

Basal Ig/Ig Signals Trigger the Coordinated Initiation of Pre-B Cell Antigen Receptor-Dependent Processes¹

Ezequiel M. Fuentes-Pananá^*, Gregory Bannish^*, Neelima Shah and John G. Monroe^2,*

^* Department of Pathology and Laboratory Medicine, and Biomedical Imaging Core Facility, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

The pro-B to pre-B transition during B cell development is dependent upon surface expression of a signaling competent pre-B cell Ag receptor (pre-BCR). Although the mature form of the BCR requires ligand-induced aggregation to trigger responses, the requirement for ligand-induced pre-BCR aggregation in promoting B cell development remains a matter of significant debate. In this study, we used transmission electron microscopy on murine primary pro-B cells and pre-B cells to analyze the aggregation state of the pre-BCR. Although aggregation can be induced and visualized following cross-linking by Abs to the pre-BCR complex, our analyses indicate that the pre-BCR is expressed on the surface of resting cells primarily in a nonaggregated state. To evaluate the degree to which basal signals mediated through nonaggregated pre-BCR complexes can promote pre-BCR-dependent processes, we used a surrogate pre-BCR consisting of the cytoplasmic regions of Ig/Ig that is targeted to the inner leaflet of the plasma membrane of primary pro-B cells. We observed enhanced proliferation in the presence of low IL-7, suppression of V_H(D)J_H recombination, and induced light (L) chain recombination and cytoplasmic L chain protein expression. Interestingly, Ig/Ig-mediated allelic exclusion was restricted to the B cell lineage as we observed normal TCR expression on CD8-expressing splenocytes. This study directly demonstrates that basal signaling initiated through Ig/Ig-containing complexes facilitates the coordinated control of differentiation events that are associated with the pre-BCR-dependent transition through the pro-B to pre-B checkpoint. Furthermore, these results argue that pre-BCR aggregation is not a requirement for pre-BCR function.

This article has been cited by other articles:

				K. L. Hoek, G. Carlesso, E. S. Clark, and W. N. Khan Absence of Mature Peripheral B Cell Populations in Mice with Concomitant Defects in B Cell Receptor and BAFF-R Signaling J. Immunol., November 1, 2009; 183(9): 5630 - 5643. [Abstract] [Full Text] [PDF]

				M. Espeli, S. J. C. Mancini, C. Breton, F. Poirier, and C. Schiff Impaired B-cell development at the pre-BII-cell stage in galectin-1-deficient mice due to inefficient pre-BII/stromal cell interactions Blood, June 4, 2009; 113(23): 5878 - 5886. [Abstract] [Full Text] [PDF]

				L. J. Anderson and R. Longnecker EBV LMP2A provides a surrogate pre-B cell receptor signal through constitutive activation of the ERK/MAPK pathway J. Gen. Virol., July 1, 2008; 89(7): 1563 - 1568. [Abstract] [Full Text] [PDF]

				C. D. Milne, S. A. Corfe, and C. J. Paige Heparan Sulfate and Heparin Enhance ERK Phosphorylation and Mediate preBCR-Dependent Events during B Lymphopoiesis J. Immunol., March 1, 2008; 180(5): 2839 - 2847. [Abstract] [Full Text] [PDF]

				E. M. Fuentes-Panana, G. Bannish, F. G. Karnell, J. F. Treml, and J. G. Monroe Analysis of the Individual Contributions of Ig{alpha} (CD79a)- and Igbeta (CD79b)-Mediated Tonic Signaling for Bone Marrow B Cell Development and Peripheral B Cell Maturation J. Immunol., December 1, 2006; 177(11): 7913 - 7922. [Abstract] [Full Text] [PDF]

				F. B. Guloglu and C. A. J. Roman Precursor B Cell Receptor Signaling Activity Can Be Uncoupled from Surface Expression. J. Immunol., June 1, 2006; 176(11): 6862 - 6872. [Abstract] [Full Text] [PDF]

				F. B. Guloglu, E. Bajor, B. P. Smith, and C. A. J. Roman The Unique Region of Surrogate Light Chain Component {lambda}5 Is a Heavy Chain-Specific Regulator of Precursor B Cell Receptor Signaling J. Immunol., July 1, 2005; 175(1): 358 - 366. [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]

				E. Katz, M. H. Lareef, J. C. Rassa, S. M. Grande, L. B. King, J. Russo, S. R. Ross, and J. G. Monroe MMTV Env encodes an ITAM responsible for transformation of mammary epithelial cells in three-dimensional culture J. Exp. Med., February 7, 2005; 201(3): 431 - 439. [Abstract] [Full Text] [PDF]

				E. M. Fuentes-Panana, G. Bannish, D. van der Voort, L. B. King, and J. G. Monroe Ig{alpha}/Ig{beta} Complexes Generate Signals for B Cell Development Independent of Selective Plasma Membrane Compartmentalization J. Immunol., February 1, 2005; 174(3): 1245 - 1252. [Abstract] [Full Text] [PDF]