Biology Reference
In-Depth Information
B cell activation
with norepinephrine
B cell activation
CD40
CD40
β
2
AR
β
2
AR
IL-4R
NE
IL-4R
Adenylate
cyclase
cAMP
Class switch
recombination
Class switch
recombination
PKA
pCREB
3
′
IgH
enhancer
activity
Production
of IgG1
Increased
production of IgG1
Figure 5.5 Signaling intermediates activated in a B cell by
2
AR stimulation.
In the
absence of
2
AR stimulation, B cell activation induces class switch recombination that
results in the production of IgG
1
. When NE is released, the
2
AR is stimulated and activates
a signaling pathway inside the cell. This pathway includes the activation of the enzyme
adenylate cyclase, an increase in intracellular cAMP levels, and activation of PKA, which
allows the targeted phosphorylation of downstream signaling intermediates and transcription
factors that alter gene expression to regulate the activity of the 3IgH-enhancer. This enhancer
region controls the rate at which antibody transcription occurs to increase the level of IgG
1
or
IgE produced per cell, without affecting the number of cells that switch to secrete IgG
1
.
stimulation with CD28 activated another signaling pathway in the B cell that up-
regulated the transcription factor Oct-2, which also regulated the level of 3-IgH
enhancer activity
[141,142]
. CD86 stimulation was also shown to increase the level
of Oct-2 binding to the 3-IgH enhancer
[141]
, allowing a cooperative binding of
the elevated levels of both OCA-B and Oct-2 to the 3-IgH enhancer region to fur-
ther increase the rate at which IgG
1
mRNA was produced
[141]
. For a more detailed
description of how an understanding of the role played by the
2
AR in enhancing
the IgG
1
response led to the discovery of the signaling pathway activated by CD86
(which had been considered devoid of signaling ability), please refer to the following
review
[143]
and subsequent signaling studies
[144,145]
.
Taken together, these findings suggested that NE exerts a regulatory effect on the
level of IgG
1
produced by enhancing the endogenous activity of the B cells that were
activated to generate the response. These findings also suggested that signaling pathways
