Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 159

3.12.4 B-Cell Activation and Signaling

Mature B lymphocytes are activated by antigen binding to B-cell receptors that
trigger various signaling cascades. 165 B-cell receptors are needed for the survival
of B lymphocytes, whatever the developmental stages. B-cell receptors may yield
constitutive, low-level, tonic signals that bypass ITAM motif phosphorylation [ 288 ].
B lymphocytes recognize both soluble antigens and antigens attached on the surface
of antigen-presenting cells [ 288 ].
Then, B-cell receptors cluster independently of activated signaling axes under the
control of B-cell coreceptors and initiate signaling. Inactive BCR dimers can coexist
with active BCR monomers [ 288 ]. Crosslinking between BCRs is dispensable, as a
single antigen-committed BCR triggers signaling. Clusters of BCRs grow with time
after antigen binding. The formation of BCR oligomers reduces their motility in the
plasma membrane.
B-cell receptor responses are regulated by various coreceptors, such as IgG
receptor Fc

R2b, a potent inhibitor of BCR signaling, and CD19, a component
of the B-cell coreceptor and a BCR activator. Receptor Fc

γ

R2b reverses the action
of BCR-activated PI3K, as it recruits the lipid phosphatase SHIP to the coligated
complex [ 288 ]. Molecule CD19 is phosphorylated in response to BCR-antigen
binding. It then acts as an adaptor that recruits guanine nucleotide-exchange factor
Vav, phosphatidylinositol 3-kinase, and protein Tyr kinase Lyn to enhance BCR
signaling. In addition, CD19 can complex with the complement component receptor
CR2 166 to enable complement-coupled antigen to connect to both the CD19-CR2
complex and B-cell receptor [ 288 ].
Upon antigen binding, ITAM motif of B-cell receptor is phosphorylated primar-
ily by recruited Lyn kinase and then spleen Tyr kinase (SYK) [ 288 ]. The growth of
BCR cluster beyond a certain size requires Lyn and SYK activity.
B lymphocytes engage antigen via membrane protrusions that provoke the
formation of BCR clusters and an immune synapse [ 288 ]. Membrane protrusion
in response to membrane-bound antigens relies on the cooperative action of
phospholipase-C

γ

γ 2, Vav guanine nucleotide-exchange factor, and Rac2 and Rap

GTPases.

165 A B-cell receptor comprises a surface-bound immunoglobulin (IgD or IgM) and transmem-
brane, Ig

heterodimer for signal transduction, as their intracellular domains contain an
immunoreceptor tyrosine-based activation motif (ITAM). A typical B lymphocyte can display
O [10 4 ]) immunoglobulins on its surface.
166 A.k.a. C3d complement component receptor (C3dR) and CD21.

α -Ig β