1. Antiviral CD19+CD27+ Memory B Cells Are Associated with Protection from Recurrent Asymptomatic Ocular Herpesvirus Infection
- Author
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Dhanushkodi, Nisha R, Prakash, Swayam, Srivastava, Ruchi, Coulon, Pierre-Gregoire A, Arellano, Danielle, Kapadia, Rayomand V, Fahim, Raian, Suzer, Berfin, Jamal, Leila, Vahed, Hawa, and BenMohamed, Lbachir
- Subjects
Immunization ,Sexually Transmitted Infections ,Infectious Diseases ,Biotechnology ,Rare Diseases ,Neurosciences ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Animals ,Antigens ,CD19 ,Herpes Simplex ,Herpesvirus 1 ,Human ,Immunity ,Immunoglobulin A ,Immunoglobulin G ,Keratitis ,Herpetic ,Memory B Cells ,Mice ,Reinfection ,Trigeminal Ganglion ,Tumor Necrosis Factor Receptor Superfamily ,Member 7 ,Virus Activation ,B memory cells ,plasma cells ,ocular herpes ,asymptomatic herpes ,virus-specific B cell ,Biological Sciences ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Virology - Abstract
Reactivation of herpes simplex virus 1 (HSV-1) from latently infected neurons of the trigeminal ganglia (TG) leads to blinding recurrent herpetic disease in symptomatic (SYMP) individuals. Although the role of T cells in herpes immunity seen in asymptomatic (ASYMP) individuals is heavily explored, the role of B cells is less investigated. In the present study, we evaluated whether B cells are associated with protective immunity against recurrent ocular herpes. The frequencies of circulating HSV-specific memory B cells and of memory follicular helper T cells (CD4+ Tfh cells), which help B cells produce antibodies, were compared between HSV-1-infected SYMP and ASYMP individuals. The levels of IgG/IgA and neutralizing antibodies were compared in SYMP and ASYMP individuals. We found that (i) the ASYMP individuals had increased frequencies of HSV-specific CD19+CD27+ memory B cells, and (ii) high frequencies of HSV-specific switched IgG+CD19+CD27+ memory B cells detected in ASYMP individuals were directly proportional to high frequencies of CD45R0+CXCR5+CD4+ memory Tfh cells. However, no differences were detected in the level of HSV-specific IgG/IgA antibodies in SYMP and ASYMP individuals. Using the UV-B-induced HSV-1 reactivation mouse model, we found increased frequencies of HSV-specific antibody-secreting plasma HSV-1 gD+CD138+ B cells within the TG and circulation of ASYMP mice compared to those of SYMP mice. In contrast, no significant differences in the frequencies of B cells were found in the cornea, spleen, and bone-marrow. Our findings suggest that circulating antibody-producing HSV-specific memory B cells recruited locally to the TG may contribute to protection from symptomatic recurrent ocular herpes. IMPORTANCE Reactivation of herpes simplex virus 1 (HSV-1) from latently infected neurons of the trigeminal ganglia (TG) leads to blinding recurrent herpetic disease in symptomatic (SYMP) individuals. Although the role of T cells in herpes immunity against blinding recurrent herpetic disease is heavily explored, the role of B cells is less investigated. In the present study, we found that in both asymptomatic (ASYMP) individuals and ASYMP mice, there were increased frequencies of HSV-specific memory B cells that were directly proportional to high frequencies of memory Tfh cells. Moreover, following UV-B-induced reactivation, we found increased frequencies of HSV-specific antibody-secreting plasma B cells within the TG and circulation of ASYMP mice compared to those of SYMP mice. Our findings suggest that circulating antibody-producing HSV-specific memory B cells recruited locally to the TG may contribute to protection from recurrent ocular herpes.
- Published
- 2022