Absence of N addition facilitates B cell development, but impairs immune responses

Robert Schelonka, Ivaylo I. Ivanov, Andre M. Vale, Reed A. Dimmitt, Mahnaz Khaled, Harry W. Schroeder

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 a-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 antiphosphorylcholine 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.

Original languageEnglish (US)
Pages (from-to)599-609
Number of pages11
JournalImmunogenetics
Volume63
Issue number9
DOIs
StatePublished - Sep 2011

Fingerprint

DNA Nucleotidylexotransferase
B-Lymphocytes
Bone Marrow
T-Lymphocytes
Immunocompetence
Antigens
Enterobacter cloacae
Haptens
Population Growth
Viral Tumor Antigens
Peritoneal Cavity
Immunocompromised Host
Humoral Immunity
Fetal Development
T-Cell Antigen Receptor
Streptococcus pneumoniae
Transcriptional Activation
Genetic Recombination
Immunoglobulins
Spleen

Keywords

  • B cell development
  • Immune responses
  • Mice
  • Terminal deoxynucleotidyl transferase

ASJC Scopus subject areas

  • Immunology
  • Genetics

Cite this

Schelonka, R., Ivanov, I. I., Vale, A. M., Dimmitt, R. A., Khaled, M., & Schroeder, H. W. (2011). Absence of N addition facilitates B cell development, but impairs immune responses. Immunogenetics, 63(9), 599-609. https://doi.org/10.1007/s00251-011-0543-7

Absence of N addition facilitates B cell development, but impairs immune responses. / Schelonka, Robert; Ivanov, Ivaylo I.; Vale, Andre M.; Dimmitt, Reed A.; Khaled, Mahnaz; Schroeder, Harry W.

In: Immunogenetics, Vol. 63, No. 9, 09.2011, p. 599-609.

Research output: Contribution to journalArticle

Schelonka, R, Ivanov, II, Vale, AM, Dimmitt, RA, Khaled, M & Schroeder, HW 2011, 'Absence of N addition facilitates B cell development, but impairs immune responses', Immunogenetics, vol. 63, no. 9, pp. 599-609. https://doi.org/10.1007/s00251-011-0543-7
Schelonka, Robert ; Ivanov, Ivaylo I. ; Vale, Andre M. ; Dimmitt, Reed A. ; Khaled, Mahnaz ; Schroeder, Harry W. / Absence of N addition facilitates B cell development, but impairs immune responses. In: Immunogenetics. 2011 ; Vol. 63, No. 9. pp. 599-609.
@article{3fd05a205ebc442bab1345e450c87c34,
title = "Absence of N addition facilitates B cell development, but impairs immune responses",
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 a-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 antiphosphorylcholine 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 = "B cell development, Immune responses, Mice, Terminal deoxynucleotidyl transferase",
author = "Robert Schelonka and Ivanov, {Ivaylo I.} and Vale, {Andre M.} and Dimmitt, {Reed A.} and Mahnaz Khaled and Schroeder, {Harry W.}",
year = "2011",
month = "9",
doi = "10.1007/s00251-011-0543-7",
language = "English (US)",
volume = "63",
pages = "599--609",
journal = "Immunogenetics",
issn = "0093-7711",
publisher = "Springer Verlag",
number = "9",

}

TY - JOUR

T1 - Absence of N addition facilitates B cell development, but impairs immune responses

AU - Schelonka, Robert

AU - Ivanov, Ivaylo I.

AU - Vale, Andre M.

AU - Dimmitt, Reed A.

AU - Khaled, Mahnaz

AU - Schroeder, Harry W.

PY - 2011/9

Y1 - 2011/9

N2 - 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 a-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 antiphosphorylcholine 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.

AB - 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 a-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 antiphosphorylcholine 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.

KW - B cell development

KW - Immune responses

KW - Mice

KW - Terminal deoxynucleotidyl transferase

UR - http://www.scopus.com/inward/record.url?scp=80053326946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053326946&partnerID=8YFLogxK

U2 - 10.1007/s00251-011-0543-7

DO - 10.1007/s00251-011-0543-7

M3 - Article

VL - 63

SP - 599

EP - 609

JO - Immunogenetics

JF - Immunogenetics

SN - 0093-7711

IS - 9

ER -