Biology Reference
In-Depth Information
4.3. Reactivation of development
In some cases, na¨ve cells of the immune system can become activated and
this potentiates additional developmental programs. Although considered to
have reached maturity, properly activated B or T lymphocytes can continue
to differentiate into effector cells or long-lived memory cells. In such cases, a
productive immune response can license a continuation in lymphocyte
development and lifespan and miRNAs have also been linked to these
later stages of development.
B lymphocytes must recognize cognate antigens and receive the neces-
sary costimulatory signals in order to develop into antibody-secreting
plasma cells. This process occurs in the germinal center (GC) of lymph
nodes and spleen and involves both Ig class switching and affinity matura-
tion of the antigen receptor. A fraction of B cells develop into long-lived
memory cells ready to mount a secondary response. miR-155 has been
shown to promote GC formation and class switching to IgG and recall
responses are diminished in miR-155
mice (
Rodriguez
et al
., 2007
;
Thai
et al
., 2007
;
Vigorito
et al
., 2007
). This involves repression of the miR-
155 targets Pu.1 and Aicda (
Dorsett
et al
., 2008
;
Rodriguez
et al
., 2007
;
Thai
et al
., 2007
;
Vigorito
et al
., 2007
). In distinction to this role for miR-155,
there is evidence that miR-125b inhibits the GC response and terminal
differentiation of B cells by repression of Blimp1 and IRF4 (
Gururajan
et al
.,
2010
).
T lymphocytes also continue their developmental programs following
antigen encounter and proper costimulation. Na¨ve helper CD4
/
T cells
can be skewed into different effector subsets including Th1, Th2, and Th17,
which promote distinct types of immune responses. miR-155 impacts these
choices and this influence involves repression of the transcription factor
cMaf and likely other targets that have yet to be defined (
Rodriguez
et al
.,
2007
). Loss-of-function studies have found that miR-155 is necessary for
adequate differentiation into Th1 and Th17 cell types
in vivo
(
O'Connell
et al
., 2010b
), while miR-155
/
CD4
þ
T cells exhibit a Th2 bias
in vitro
(
Rodriguez
et al
., 2007
;
Thai
et al
., 2007
). Th17 development is
also regulated by miR-326 which represses Ets1, an established negative
regulator of the Th17 lineage (
Du
et al
., 2009
).
þ
5. MicroRNAs During Hematopoietic
Stress and Disease
Breakdowns in the hematopoietic development process or in cellular
functioning are underlying causes of hematopoietic disease, and these can be
initiated by inflammatory stress, mutations in cells of a specific lineage, or
