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 Related articles in The JI 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 Middendorp, S. Articles by Hendriks, R. W. Search for Related Content PubMed PubMed Citation Articles by Middendorp, S. Articles by Hendriks, R. W.

Cellular Maturation Defects in Bruton’s Tyrosine Kinase-Deficient Immature B Cells Are Amplified by Premature B Cell Receptor Expression and Reduced by Receptor Editing¹

Department of Immunology, Erasmus MC Rotterdam, Rotterdam, The Netherlands

In the mouse, Bruton’s tyrosine kinase (Btk) is essential for efficient developmental progression of CD43⁺CD2^- large cycling into CD43^-CD2⁺ small resting pre-B cells in the bone marrow and of IgM^high transitional type 2 B cells into IgM^low mature B cells in the spleen. In this study, we show that the impaired induction of cell surface changes in Btk-deficient pre-B cells was still noticeable in ⁺ immature B cells, but was largely corrected in ⁺ immature B cells. As gene rearrangements are programmed to follow rearrangements and expression is associated with receptor editing, we hypothesized that the transit time through the pre-B cell compartment or receptor editing may affect the extent of the cellular maturation defects in Btk-deficient B cells. To address this issue, we used 3-83µ transgenic mice, which prematurely express a complete B cell receptor and therefore manifest accelerated B cell development. In Btk-deficient 3-83µ mice, the IgM⁺ B cells in the bone marrow exhibited a very immature phenotype (pre-BCR⁺CD43⁺CD2^-) and were arrested at the transitional type 1 B cell stage upon arrival in the spleen. However, these cellular maturation defects were largely restored when Btk-deficient 3-83µ B cells were on a centrally deleting background and therefore targeted for receptor editing. Providing an extended time window for developing B cells by enforced expression of the antiapoptotic gene Bcl-2 did not alter the Btk dependence of their cellular maturation. We conclude that premature B cell receptor expression amplifies the cellular maturation defects in Btk-deficient B cells, while extensive receptor editing reduces these defects.

Related articles in The JI:

IN THIS ISSUE

The JI 2004 172: 1331-1332. [Full Text]  

This article has been cited by other articles:

				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]

				Z. S. M. Rahman and T. Manser B Cells Expressing Bcl-2 and a Signaling-Impaired BAFF-Specific Receptor Fail to Mature and Are Deficient in the Formation of Lymphoid Follicles and Germinal Centers J. Immunol., November 15, 2004; 173(10): 6179 - 6188. [Abstract] [Full Text] [PDF]

				Y.-S. Ng, H. Wardemann, J. Chelnis, C. Cunningham-Rundles, and E. Meffre Bruton's Tyrosine Kinase Is Essential for Human B Cell Tolerance J. Exp. Med., October 4, 2004; 200(7): 927 - 934. [Abstract] [Full Text] [PDF]