Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 157

component C1q, as it stimulates their engulfment by phagocytes. 159 It also in-
creases the presentation of pathogen-derived antigens. Furthermore, it facilitates the
removal of apoptotic cells [ 287 ].
Natural S IgM is particularly secreted by peritoneal B1 lymphocytes [ 287 ]. It
recognizes and binds self antigens such as phospholipids. It interacts with members
of the complement system, mannose-binding lectin, and IgM-devoted Fc receptors
(Fc R expressed by follicular dendritic cells, macrophages,

and B cells that bind both IgA and IgM). Natural IgM promotes the generation of
mature B cells in the spleen, but reduces the survival of peritoneal B1a cells [ 287 ].
B-cell receptors are members of the family of multichain immune-recognition
receptors (MIRR) involved in adaptive immunity that also includes T-cell receptors
and the high-affinity receptor for IgE (Fc

RaswellasFc α -Fc

R1) [ 288 ]. These receptors localize to
membrane rafts. The engagement of antigens by BCR, TCR, and Fc

R1 causes

receptor clustering for signaling. 160

3.12.3.1 Antibody Diversification

Clonal selection of specific B cells results from antigen binding to B-cell receptors
owing to somatic hypermutation and class switching. In cooperation with helper
T cells and cells of the innate immunity, antigens provoke proliferation and differ-
entiation of naive B cells into memory B cells and antibody-secreting plasmocytes.
Maturation with increased antibody affinity and class switching occur at the earliest
step of BCR signaling [ 288 ].
Antibody diversification enables the humoral response. B lymphocytes diversify
their antibody repertoire via genetic modifications during 2 distinct phases of
B-cell maturation. In the antigen-independent phase of B-cell maturation , B-cell
precursors in the bone marrow generate antigen recognition diversity by assembling
exons that encode variable immunoglobulin heavy and light chains via gene
recombination. Plasmalemmal IgM is then expressed by new B lymphocytes. After
further stages of differentiation and expression of IgD, B lymphocytes exit from the
bone marrow and migrate to secondary lymphoid organs, where they initiate the
antigen-dependent phase of B-cell development .
In the presence of antigen, mature B lymphocytes in germinal centers of
secondary lymphoid follicles diversify their antibody repertoire via somatic hyper-
mutation and class switching [ 271 ]. 161

159 Monomeric IgM does not bind complement component C1q.
160 Antigen-engaged TCR clusters recruit leukocyte-specific cytosolic Tyr kinase (LCK), TCR
coreceptor CD2, and adaptor Linker for activation of T cells (LAT). Antigen-committed BCR
clusters attract spleen Tyr kinase (SYK).
161 During an immune response, B lymphocytes in germinal centers undergo somatic hypermu-
tation that introduces point mutations at high rates into the variable regions of immunoglobulin
genes, thereby allowing selection of B cells with higher antibody affinity. Mature B lymphocytes
also sustain class-switch recombination to rearrange DNA segments encoding the constant region