Rgs13 constrains early B cell responses and limits germinal center sizes.

Germinal centers (GCs) are microanatomic structures that develop in secondary lymphoid organs in response to antigenic stimulation. Within GCs B cells clonally expand and their immunoglobulin genes undergo class switch recombination and somatic hypermutation. Transcriptional profiling has identified a number of genes that are prominently expressed in GC B cells. Among them is Rgs13, which encodes an RGS protein with a dual function. Its canonical function is to accelerate the intrinsic GTPase activity of heterotrimeric G-protein α subunits at the plasma membrane, thereby limiting heterotrimeric G-protein signaling. A unique, non-canonical function of RGS13 occurs following translocation to the nucleus, where it represses CREB transcriptional activity. The functional role of RGS13 in GC B cells is unknown. To create a surrogate marker for Rgs13 expression and a loss of function mutation, we inserted a GFP coding region into the Rgs13 genomic locus. Following immunization GFP expression rapidly increased in activated B cells, persisted in GC B cells, but declined in newly generated memory B and plasma cells. Intravital microscopy of the inguinal lymph node (LN) of immunized mice revealed the rapid appearance of GFP(+) cells at LN interfollicular regions and along the T/B cell borders, and eventually within GCs. Analysis of WT, knock-in, and mixed chimeric mice indicated that RGS13 constrains extra-follicular plasma cell generation, GC size, and GC B cell numbers. Analysis of select cell cycle and GC specific genes disclosed an aberrant gene expression profile in the Rgs13 deficient GC B cells. These results indicate that RGS13, likely acting at cell membranes and in nuclei, helps coordinate key decision points during the expansion and differentiation of naive B cells..

Medienart:

E-Artikel

Erscheinungsjahr:

2013

Erschienen:

2013

Enthalten in:

Zur Gesamtaufnahme - volume:8

Enthalten in:

PLoS ONE - 8(2013), 3, p e60139

Sprache:

Englisch

Beteiligte Personen:

Il-Young Hwang [VerfasserIn]
Kyung-Sun Hwang [VerfasserIn]
Chung Park [VerfasserIn]
Kathleen A Harrison [VerfasserIn]
John H Kehrl [VerfasserIn]

Links:

doi.org [kostenfrei]
doaj.org [kostenfrei]
europepmc.org [kostenfrei]
Journal toc [kostenfrei]

Themen:

Medicine
Q
R
Science

doi:

10.1371/journal.pone.0060139

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

DOAJ04470240X