AUTHOR=Zhao Rongqing , Zhang Huihui , Zhang Yan , Li Dan , Huang Chuanxin , Li Fubin 

TITLE=In vivo Screen Identifies Zdhhc2 as a Critical Regulator of Germinal Center B Cell Differentiation

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01025

DOI=10.3389/fimmu.2020.01025

ISSN=1664-3224

ABSTRACT=<p>Germinal center (GC) B cell differentiation is critical for the production of affinity-matured pathogen-specific antibodies, the dysregulation of which may lead to humoral immunodeficiency or autoimmunity. The development of an <italic>in vivo</italic> screening system for factors regulating GC B cell differentiation has been a challenge. Here we describe a small-scale <italic>in vivo</italic> screening system with NP-specific B1-8<sup>hi</sup> cells and a retroviral shRNA library targeting 78 candidate genes to search for B cell-intrinsic factors that specifically regulate GC B cell differentiation. <italic>Zdhhc2</italic>, a gene encoding palmitoyltransferase ZDHHC2 and highly expressed in GC B cells, is identified as a strong positive regulator of GC B cell differentiation. B1-8<sup>hi</sup> cells transduced with <italic>Zdhhc2</italic>-shRNA are severely compromised in differentiating into GC B cells. A further analysis of <italic>in vitro</italic> differentiated B cells transduced with <italic>Zdhhc2</italic>-shRNA shows that <italic>Zdhhc2</italic> is critical for the proliferation and the survival of B cells stimulated by CD40L, BAFF, and IL-21 and consequently impacts on their differentiation into GC B cells and post-GC B cells. These studies not only identify <italic>Zdhhc2</italic> as a novel regulator of GC B cell differentiation but also represent a proof of concept of <italic>in vivo</italic> screen for regulators of GC B cell differentiation.</p>