TitleThe BCL6 RD2 domain governs commitment of activated B cells to form germinal centers.
Publication TypeJournal Article
Year of Publication2014
AuthorsHuang, ChuanXin, Gonzalez David G., Cote Christine M., Jiang Yanwen, Hatzi Katerina, Teater Matt, Dai Kezhi, Hla Timothy, Haberman Ann M., and Melnick Ari
JournalCell Rep
Date Published2014 Sep 11
KeywordsAnimals, B-Lymphocytes, Cell Movement, Cytokines, DNA-Binding Proteins, Germinal Center, Histone Deacetylase 2, Lymphocyte Activation, Mice, Mutation, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins c-bcl-6, Receptors, G-Protein-Coupled, Receptors, Lysosphingolipid, Sphingosine-1-Phosphate Receptors, T-Lymphocytes, Helper-Inducer

<p>To understand how the Bcl6 transcriptional repressor functions in the immune system, we disrupted its RD2 repression domain in mice. Bcl6RD2(MUT) mice exhibit a complete loss of germinal center (GC) formation but retain normal extrafollicular responses. Bcl6RD2(MUT) antigen-engaged B cells migrate to the interfollicular zone and interact with cognate T helper cells. However, these cells fail to complete early GC-commitment differentiation and coalesce as nascent GC aggregates. Bcl6 directly binds and represses trafficking receptors S1pr1 and Gpr183 by recruiting Hdac2 through the RD2 domain. Deregulation of these genes impairs B cell migration and may contribute to GC failure in Bcl6RD2(MUT) mice. The development of functional GC-TFH cells was partially impaired in Bcl6RD2(MUT) mice. In contrast to Bcl6(-/-) mice, Bcl6RD2(MUT) animals experience no inflammatory disease or macrophage deregulation. These results reveal an essential role for RD2 repression in early GC commitment and striking biochemical specificity in Bcl6 control of humoral and innate immune-cell phenotypes.</p>

Alternate JournalCell Rep
PubMed ID25176650
PubMed Central IDPMC4163070
Grant ListR21 AI101704 / AI / NIAID NIH HHS / United States
R01 AI080850 / AI / NIAID NIH HHS / United States
P30 AR053495 / AR / NIAMS NIH HHS / United States
R21AI101704 / AI / NIAID NIH HHS / United States
R01AI080850 / AI / NIAID NIH HHS / United States
R01 CA104348 / CA / NCI NIH HHS / United States
NCI R01 104348 / / PHS HHS / United States
R01 CA143032 / CA / NCI NIH HHS / United States