TY - JOUR
T1 - Gammaherpesvirus-infected germinal center cells express a distinct immunoglobulin repertoire
AU - Zelazowska, Monika A.
AU - Dong, Qiwen
AU - Plummer, Joshua B.
AU - Zhong, Yi
AU - Liu, Bin
AU - Krug, Laurie T.
AU - McBride, Kevin M.
N1 - Funding Information:
We acknowledge Laurie Levine in Stony Brook University (SBU) Division of Laboratory Animal Resources for assistance with husbandry, and the SBU flow cytometry facility. We thank Samuel Speck for providing the MHV68-H2BYFP bacterial artificial chromosome. This work was supported by National Institutes of Health (NIH) AI125397 and AI111129 and the Three Strohm Sisters Family Foundation. We acknowledge the University of Texas MD Anderson Cancer Center (UTMDACC) Research Animal Support Facility (P30 NIH CA16672) and Center for Cancer Epigenetics. Cancer Prevention and Research Institute of Texas (CPRIT) Core Facility Support Grants to UTMDACC flow cytometry and cell imaging core (CPRIT RP170628), UTMDACC Science Park Next Generation Sequencing Core (CPRIT RP120348 and CPRIT RP170002) and UTMDACC Recombinant antibody production core (CPRIT RP190507).
Publisher Copyright:
© 2020 Rockefeller University Press. All rights reserved.
PY - 2020
Y1 - 2020
N2 - The gammaherpesviruses (γHVs), human Kaposi sarcoma-associated herpesvirus (KSHV), EBV, and murine γHV68 are prevalent infections associated with lymphocyte pathologies. After primary infection, EBV and γHV68 undergo latent expansion in germinal center (GC) B cells and persists in memory cells. The GC reaction evolves and selects antigen-specific B cells for memory development but whether γHV passively transients or manipulates this process in vivo is unknown. Using the γHV68 infection model, we analyzed the Ig repertoire of infected and uninfected GC cells from individual mice. We found that infected cells displayed the hallmarks of affinity maturation, hypermutation, and isotype switching but underwent clonal expansion. Strikingly, infected cells displayed distinct repertoire, not found in uninfected cells, with recurrent utilization of certain Ig heavy V segments including Ighv10-1. In a manner observed with KSHV, γHV68 infected cells also displayed lambda light chain bias. Thus, γHV68 subverts GC selection to expand in a specific B cell subset during the process that develops long-lived immunologic memory.
AB - The gammaherpesviruses (γHVs), human Kaposi sarcoma-associated herpesvirus (KSHV), EBV, and murine γHV68 are prevalent infections associated with lymphocyte pathologies. After primary infection, EBV and γHV68 undergo latent expansion in germinal center (GC) B cells and persists in memory cells. The GC reaction evolves and selects antigen-specific B cells for memory development but whether γHV passively transients or manipulates this process in vivo is unknown. Using the γHV68 infection model, we analyzed the Ig repertoire of infected and uninfected GC cells from individual mice. We found that infected cells displayed the hallmarks of affinity maturation, hypermutation, and isotype switching but underwent clonal expansion. Strikingly, infected cells displayed distinct repertoire, not found in uninfected cells, with recurrent utilization of certain Ig heavy V segments including Ighv10-1. In a manner observed with KSHV, γHV68 infected cells also displayed lambda light chain bias. Thus, γHV68 subverts GC selection to expand in a specific B cell subset during the process that develops long-lived immunologic memory.
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U2 - 10.26508/lsa.201900526
DO - 10.26508/lsa.201900526
M3 - Article
C2 - 32029571
AN - SCOPUS:85079082694
SN - 2575-1077
VL - 3
JO - Life science alliance
JF - Life science alliance
IS - 3
M1 - e201900526
ER -