Absence of N addition facilitates B cell development, but impairs immune responses
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ORIGINAL PAPER
Absence of N addition facilitates B cell development, but impairs immune responses Robert L. Schelonka & Ivaylo I. Ivanov & Andre M. Vale & Reed A. Dimmitt & Mahnaz Khaled & Harry W. Schroeder Jr.
Received: 21 December 2010 / Accepted: 24 May 2011 / Published online: 10 June 2011 # The Author(s) 2011. This article is published with open access at Springerlink.com
Abstract The programmed, stepwise acquisition of immunocompetence that marks the development of the fetal immune response proceeds during a period when both T cell receptor and immunoglobulin (Ig) repertoires exhibit reduced junctional diversity due to physiologic terminal deoxynucleotidyl transferase (TdT) insufficiency. To test the effect of N addition on humoral responses, we transplanted bone marrow from TdT-deficient (TdT−/−) and wild-type (TdT+/+) BALB/c mice into recombination activation gene 1-deficient BALB/c hosts. Mice transplanted with TdT−/− cells exhibited diminished humoral responses to the Tindependent antigens α-1-dextran and (2,4,6-trinitrophenyl) hapten conjugated to AminoEthylCarboxymethyl-FICOLL, to the T-dependent antigens NP19CGG and hen egg lysozyme, and to Enterobacter cloacae, a commensal bacteria that can become an opportunistic pathogen in immature and immunocompromised hosts. An exception to this pattern of reduction was the T-independent anti-
phosphorylcholine response to Streptococcus pneumoniae, which is normally dominated by the N-deficient T15 idiotype. Most of the humoral immune responses in the recipients of TdT−/− bone marrow were impaired, yet population of the blood with B and T cells occurred more rapidly. To further test the effect of N-deficiency on B cell and T cell population growth, transplanted TdT-sufficient and -deficient BALB/c IgMa and congenic TdT-sufficient CB17 IgMb bone marrow were placed in competition. TdT−/− cells demonstrated an advantage in populating the bone marrow, the spleen, and the peritoneal cavity. TdT deficiency, which characterizes fetal lymphocytes, thus appears to facilitate filling both central and peripheral lymphoid compartments, but at the cost of altered responses to a broad set of antigens. Keywords Terminal deoxynucleotidyl transferase . B cell development . Immune responses . Mice
Electronic supplementary material The online version of this article (doi:10.1007/s00251-011-0543-7) contains supplementary material, which is available to authorized users. R. L. Schelonka : R. A. Dimmitt : M. Khaled Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294, USA I. I. Ivanov : H. W. Schroeder Jr. Department of Microbiology, University of Alabama at Birmingham, Shelby Building 401, 1530 3rd Avenue South, Birmingham, AL 35294-2182, USA A. M. Vale : H. W. Schroeder Jr. (*) Department of Medicine, University of Alabama at Birmingham, Shelby Building 401, 1530 3rd Avenue South, Birmingham, AL 35294-2182, USA e-mail: [email protected]
H. W. Schroeder Jr. Department of Genetics, University of Alabama at Birmingham, Shelby Building 401, 1530 3rd Avenue
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