B cells, antibody-secreting cells, and virus-specific antibodies respond to herpes simplex virus 2 reactivation in skin

J Clin Invest. 2021 May 3;131(9):e142088. doi: 10.1172/JCI142088.

Abstract

Tissue-based T cells are important effectors in the prevention and control of mucosal viral infections; less is known about tissue-based B cells. We demonstrate that B cells and antibody-secreting cells (ASCs) are present in inflammatory infiltrates in skin biopsy specimens from study participants during symptomatic herpes simplex virus 2 (HSV-2) reactivation and early healing. Both CD20+ B cells, most of which are antigen inexperienced based on their coexpression of IgD, and ASCs - characterized by dense IgG RNA expression in combination with CD138, IRF4, and Blimp-1 RNA - were found to colocalize with T cells. ASCs clustered with CD4+ T cells, suggesting the potential for crosstalk. HSV-2-specific antibodies to virus surface antigens were also present in tissue and increased in concentration during HSV-2 reactivation and healing, unlike in serum, where concentrations remained static over time. B cells, ASCs, and HSV-specific antibody were rarely detected in biopsies of unaffected skin. Evaluation of samples from serial biopsies demonstrated that B cells and ASCs followed a more migratory than resident pattern of infiltration in HSV-affected genital skin, in contrast to T cells. Together, these observations suggest the presence of distinct phenotypes of B cells in HSV-affected tissue; dissecting their role in reactivation may reveal new therapeutic avenues to control these infections.

Keywords: Adaptive immunity; Beta cells; Immunoglobulins; Immunology; Infectious disease.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes
  • Female
  • Herpes Simplex / immunology*
  • Herpes Simplex / pathology
  • Herpesvirus 2, Human / physiology*
  • Humans
  • Immunoglobulin D / immunology*
  • Immunoglobulin G / immunology*
  • Male
  • Skin / immunology*
  • Skin / pathology
  • Skin / virology
  • Virus Activation / immunology*

Substances

  • Antibodies, Viral
  • Immunoglobulin D
  • Immunoglobulin G