Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV-1 envelope proteins are largely mediated via human CD5+ B cells

Authors

  • Subhabrata Biswas,

    1. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute
    2. Department of Medicine, Harvard Medical School, Boston, MA
    Search for more papers by this author
  • Hong Chang,

    1. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute
    2. Department of Medicine, Harvard Medical School, Boston, MA
    Search for more papers by this author
    • Present address: Department of Biochemistry, School of Basic Medicine, Hebei Medical University, Shijiazhuang 050091, China.

  • Phuong T. N. Sarkis,

    1. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute
    2. Department of Medicine, Harvard Medical School, Boston, MA
    Search for more papers by this author
  • Erol Fikrig,

    1. Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
    Search for more papers by this author
  • Quan Zhu,

    1. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute
    2. Department of Medicine, Harvard Medical School, Boston, MA
    Search for more papers by this author
  • Wayne A. Marasco

    1. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute
    2. Department of Medicine, Harvard Medical School, Boston, MA
    Search for more papers by this author

Errata

This article is corrected by:

  1. Errata: Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV-1 envelope proteins are largely mediated via human CD5+ B cells Volume 136, Issue 3, 361, Article first published online: 1 June 2012

Dr W. A. Marasco, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, JFB824, Boston, MA 02215, USA. Email: wayne_marasco@dfci.harvard.edu
Senior author: Wayne A. Marasco

Summary

BLT mice, constructed by surgical implantation of human fetal thymus–liver tissues and intravenous delivery of autologous CD34+ haematopoietic stem cells into adult non-obese diabetic/severe combined immunodeficiency mice, were evaluated for vaccine-induced humoral immune responses. Following engraftment, these mice developed a human lymphoid system; however, the majority of the peripheral human B lymphocytes displayed an immature phenotype as evidenced by surface CD10 expression. Over 50% of the human B cells in the periphery but not in the bone marrow also expressed the CD5 antigen, which is found only infrequently on mature follicular B cells in humans. A single intramuscular immunization with recombinant viral envelope antigens, e.g. HIVgp140 and West Nile Virus envelope proteins, together with the immune stimulatory IC31® adjuvant resulted in seroconversion characterized by antigen-specific human antibodies predominantly of the IgM isotype. However, repeated booster immunizations did not induce secondary immune responses as evidenced by the lack of class switching and specific IgM levels remaining relatively unchanged. Interestingly, the peripheral CD19+ CD5+ but not the CD19+ CD5 human B lymphocytes displayed a late developing CD27+ IgM+ memory phenotype, suggesting that the CD5+ B-cell subset, previously implicated in ‘natural antibody’ production, may play a role in the vaccine-induced antibody response. Furthermore, human T lymphocytes from these mice demonstrated suboptimal proliferative responses and loss of co-stimulatory surface proteins ex vivo that could be partially reversed with human interleukin-2 and interleukin-7. Therefore, vaccine-induced immune responses in BLT mice resemble a T-cell-independent pathway that can potentially be modulated in vivo by the exogenous delivery of human cytokines/growth factors.

Ancillary