PMID- 34985998
OWN - NLM
STAT- MEDLINE
DCOM- 20220428
LR  - 20220910
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 96
IP  - 5
DP  - 2022 Mar 9
TI  - Antiviral CD19(+)CD27(+) Memory B Cells Are Associated with Protection from 
      Recurrent Asymptomatic Ocular Herpesvirus Infection.
PG  - e0205721
LID - 10.1128/jvi.02057-21 [doi]
LID - e02057-21
AB  - 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(+) T(fh) 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 T(fh) 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 
      T(fh) 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.
FAU - Dhanushkodi, Nisha R
AU  - Dhanushkodi NR
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      University of California Irvine, School of Medicine, Irvine, California, USA.
FAU - Prakash, Swayam
AU  - Prakash S
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      University of California Irvine, School of Medicine, Irvine, California, USA.
FAU - Srivastava, Ruchi
AU  - Srivastava R
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      University of California Irvine, School of Medicine, Irvine, California, USA.
FAU - Coulon, Pierre-Gregoire A
AU  - Coulon PA
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      University of California Irvine, School of Medicine, Irvine, California, USA.
FAU - Arellano, Danielle
AU  - Arellano D
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      University of California Irvine, School of Medicine, Irvine, California, USA.
FAU - Kapadia, Rayomand V
AU  - Kapadia RV
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      University of California Irvine, School of Medicine, Irvine, California, USA.
FAU - Fahim, Raian
AU  - Fahim R
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      University of California Irvine, School of Medicine, Irvine, California, USA.
FAU - Suzer, Berfin
AU  - Suzer B
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      University of California Irvine, School of Medicine, Irvine, California, USA.
FAU - Jamal, Leila
AU  - Jamal L
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      University of California Irvine, School of Medicine, Irvine, California, USA.
FAU - Vahed, Hawa
AU  - Vahed H
AD  - Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab 
      Partners, Irvine, California, USA.
FAU - BenMohamed, Lbachir
AU  - BenMohamed L
AUID- ORCID: 0000-0001-9468-2521
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      University of California Irvine, School of Medicine, Irvine, California, USA.
AD  - Department of Molecular Biology & Biochemistry, University Lab Partners, Irvine, 
      California, USA.
AD  - Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab 
      Partners, Irvine, California, USA.
AD  - Institute for Immunology, University of California Irvine, School of Medicine, 
      Irvine, California, USA.
LA  - eng
GR  - R41 AI138764/AI/NIAID NIH HHS/United States
GR  - R01 EY026103/EY/NEI NIH HHS/United States
GR  - R01 AI143348/AI/NIAID NIH HHS/United States
GR  - R01 EY019896/EY/NEI NIH HHS/United States
GR  - R43 AI124911/AI/NIAID NIH HHS/United States
GR  - R01 AI150091/AI/NIAID NIH HHS/United States
GR  - R01 EY014900/EY/NEI NIH HHS/United States
GR  - R21 AI143326/AI/NIAID NIH HHS/United States
GR  - R01 EY024618/EY/NEI NIH HHS/United States
GR  - R21 AI110902/AI/NIAID NIH HHS/United States
GR  - R21 AI147499/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220105
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, CD19)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Tumor Necrosis Factor Receptor Superfamily, Member 7)
SB  - IM
MH  - Animals
MH  - Antigens, CD19/immunology
MH  - *Herpes Simplex
MH  - *Herpesvirus 1, Human
MH  - Immunity/immunology
MH  - Immunoglobulin A/blood
MH  - Immunoglobulin G/blood
MH  - *Keratitis, Herpetic/immunology
MH  - *Memory B Cells/immunology/virology
MH  - Mice
MH  - *Reinfection/immunology/virology
MH  - Trigeminal Ganglion/virology
MH  - Tumor Necrosis Factor Receptor Superfamily, Member 7/immunology
MH  - Virus Activation/immunology
PMC - PMC8906405
OTO - NOTNLM
OT  - B memory cells
OT  - asymptomatic herpes
OT  - ocular herpes
OT  - plasma cells
OT  - virus-specific B cell
COIS- The authors declare no conflict of interest. The authors have declared that no 
      conflict of interest exists.
EDAT- 2022/01/06 06:00
MHDA- 2022/04/29 06:00
PMCR- 2022/09/09
CRDT- 2022/01/05 17:14
PHST- 2022/01/06 06:00 [pubmed]
PHST- 2022/04/29 06:00 [medline]
PHST- 2022/01/05 17:14 [entrez]
PHST- 2022/09/09 00:00 [pmc-release]
AID - 02057-21 [pii]
AID - jvi.02057-21 [pii]
AID - 10.1128/jvi.02057-21 [doi]
PST - ppublish
SO  - J Virol. 2022 Mar 9;96(5):e0205721. doi: 10.1128/jvi.02057-21. Epub 2022 Jan 5.