Stages of germinal center transit are defined by B cell transcription factor coexpression and relative abundance.
نویسندگان
چکیده
The transit of T cell-activated B cells through the germinal center (GC) is controlled by sequential activation and repression of key transcription factors, executing the pre- and post-GC B cell program. B cell lymphoma (BCL) 6 and IFN regulatory factor (IRF) 8 are necessary for GC formation and for its molecular activity in Pax5+PU.1+ B cells. IRF4, which is highly expressed in BCL6- GC B cells, is necessary for class switch recombination and the plasma cell differentiation at exit from the GC. In this study, we show at the single-cell level broad coexpression of IRF4 with BCL6, Pax5, IRF8, and PU.1 in pre- and post-GC B cells in human and mouse. IRF4 is down-regulated in BCL6+ human GC founder cells (IgD+CD38+), is absent in GC centroblasts, and is re-expressed in positive regulatory domain 1-positive centrocytes, which are negative for all the B cell transcription factors. Activated (CD30+) and activation-induced cytidine deaminase-positive extrafollicular blasts coexpress Pax5 and IRF4. PU.1-negative plasma cells and CD30+ blasts uniquely display the conformational epitope of IRF4 recognized by the MUM1 Ab, an epitope that is absent from any other IRF4+PU.1+ lymphoid and hemopoietic subsets. Low grade B cell lymphomas, representing the malignant counterpart of pre- and post-GC B cells, accordingly express IRF4. However, a fraction of BCL6+ diffuse large B cell lymphomas express IRF4 bearing the MUM1 epitope, indicative of a posttranscriptional modification of IRF4 not seen in the normal counterpart.
منابع مشابه
Coexpression and Relative Abundance Defined by B Cell Transcription Factor Stages of Germinal Center Transit Are
متن کامل
P-30: The Investigation of Transcript Expression Level of Mitochondrial Transcription Factor A (TFAM) during In Vitro Maturation (IVM) in Single Human Oocytes
Background In vitro maturation (IVM) of human oocytes has acquired increasing attention in infertility treatment with great promise. This technique is an alternative conventional in vitro fertilization-embryo transfer (IVF-ET), and can be reduced the side effects of gonadotropin stimulation such as ovarian hyperstimulation (OHSS). Oocyte maturation is a complex process including cytoplasmic and...
متن کاملSignatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program.
We utilized gene expression profiling of a comprehensive panel of purified developmentally defined normal murine B cells to identify unique transcriptional signatures for each subset. To elucidate transcription factor activities that function in a stage-specific fashion, we used gene sets that share transcription factor targets and found that germinal center B cells had a robust enrichment of u...
متن کاملComparison of Mitochondrial-Related Transcriptional Levels of mitochondrial transcription factor A, Nuclear respiratory factor 1 and cytochrome c oxidase subunit 1 Genes in Single Human Oocytes at Various Stages of the Oocyte Maturation
Background: The aim of the current study was to assess the mRNA levels of two mitochondria-related genes, including nuclear-encoded NRF1 (nuclear respiratory factor 1), mitochondrial transcription factor A (TFAM), and mitochondrial-encoded cytochrome c oxidase subunit 1 (MT-CO1) genes in various stages of the human oocyte maturation. Methods: Oocytes were obtained from nine infertile women wit...
متن کاملTranscription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells.
The transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into the functions of Ebf1 at distinct stages of differentiation, we conditionally inactivated Ebf1. We found that Ebf1 is required for the proliferation, survival, and signaling of pro-B cells and peripheral B-cell subsets, including B1 cells and marginal zone B cells. The proliferation defect o...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of immunology
دوره 177 10 شماره
صفحات -
تاریخ انتشار 2006