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Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes.

Publication ,  Journal Article
Holl, TM; Yang, G; Kuraoka, M; Verkoczy, L; Alam, SM; Moody, MA; Haynes, BF; Kelsoe, G
Published in: J Immunol
April 1, 2014

We have shown that the protective HIV-1 Ab, 2F5, avidly reacts with a conserved mammalian self-Ag, kynureninase, and that the development of B cells specific for the 2F5 epitope is constrained by immunological tolerance. These observations suggest that the capacity to mount Ab responses to the 2F5 epitope is mitigated by tolerance, but such capacity may be latent in the pretolerance and/or anergic B cell pools. In this study, we use B cell tetramer reagents to track the frequencies of B cells that recognize the HIV-1 2F5 epitope (SP62): in C57BL/6 mice, SP62-binding transitional B cells are readily identified in bone marrow but are lost during subsequent development. Unsurprisingly then, immunization with SP62 immunogen does not elicit significant humoral responses in normal C57BL/6 mice. Reconstitution of Rag1(null) mice with normal congenic B cells that have matured in vitro restores the capacity to mount significant serum Ab and germinal center responses to this HIV-1 epitope. These B cell cultures are permissive for the development of autoreactive B cells and support the development of SP62-specific B cell compartments normally lost in 2F5 Ab knockin mice. The recovery of humoral responses to the 2F5/SP62 epitope of HIV-1 by reconstitution with B cells containing forbidden, autoreactive clones provides direct evidence that normal C57BL/6 mice latently possess the capacity to generate humoral responses to a conserved, neutralizing HIV-1 epitope.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

April 1, 2014

Volume

192

Issue

7

Start / End Page

3269 / 3279

Location

United States

Related Subject Headings

  • Spleen
  • Protein Binding
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice, 129 Strain
  • Mice
  • Lymphocytes
  • Immunology
  • Immune Tolerance
  • HIV-1
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Holl, T. M., Yang, G., Kuraoka, M., Verkoczy, L., Alam, S. M., Moody, M. A., … Kelsoe, G. (2014). Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes. J Immunol, 192(7), 3269–3279. https://doi.org/10.4049/jimmunol.1302829
Holl, T Matt, Guang Yang, Masayuki Kuraoka, Laurent Verkoczy, S Munir Alam, M Anthony Moody, Barton F. Haynes, and Garnett Kelsoe. “Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes.J Immunol 192, no. 7 (April 1, 2014): 3269–79. https://doi.org/10.4049/jimmunol.1302829.
Holl TM, Yang G, Kuraoka M, Verkoczy L, Alam SM, Moody MA, et al. Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes. J Immunol. 2014 Apr 1;192(7):3269–79.
Holl, T. Matt, et al. “Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes.J Immunol, vol. 192, no. 7, Apr. 2014, pp. 3269–79. Pubmed, doi:10.4049/jimmunol.1302829.
Holl TM, Yang G, Kuraoka M, Verkoczy L, Alam SM, Moody MA, Haynes BF, Kelsoe G. Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes. J Immunol. 2014 Apr 1;192(7):3269–3279.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

April 1, 2014

Volume

192

Issue

7

Start / End Page

3269 / 3279

Location

United States

Related Subject Headings

  • Spleen
  • Protein Binding
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice, 129 Strain
  • Mice
  • Lymphocytes
  • Immunology
  • Immune Tolerance
  • HIV-1