Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 158

B cells can be activated independently from T cells by bacterial polysaccharides
and microorganism-derived Toll-like receptor ligands, to generate short-lived, low-
affinity, extrafollicular plasmocytes. However, interactions between T and B cells
in secondary lymphoid tissues 162 are required for antibody responses specific for
foreign antigens and generation of high-affinity memory B cells and long-lived
plasmocytes. Such a process particularly involves follicular helper T cells (T FH )that
express chemokine receptor CXCR5, 163 like activated CD4 + T cells in the tonsils

T cells in blood [ 289 ]. 164 The lymphocytes that become T cells
migrate from the bone marrow to the thymus, where they mature.

and memory CD4 +

of the immunoglobulin genes, so that B lymphocytes change antibody isotypes from IgM to IgG,
IgA, or IgE. Somatic hypermutation introduces point mutations into VHDJH and VLJL exons that
encode immunoglobulin heavy (H) and light (L) chain variable regions from individual variable
(V), diversity (D), and joining (J) gene segments. Class switching substitutes the IgH constant
region C genes (class-switch

recombination) to generate secondary IgG, IgA, and IgE that have the same antigen specificity
as IgM and IgD, but different functions. Circulating IgAs that include mostly members of the
IgA1 class are predominantly present as monomers. They bind to various receptors expressed by
granulocytes, monocytes, macrophages, dendritic cells, hepatocytes, hepatic Kupffer cells, and
renal mesangial cells. Mucosal IgAs exist as dimers and oligomers and comprise both IgA1 and
IgA2 types encoded by C α 1andC α 2 genes.
162 After binding antigen, B cells interact with activated T cells in the T-cell zones of secondary
lymphoid tissues. B cells upregulate expression of chemokine receptor CCR7 and are attracted by
a gradient of CCL21 chemokine to the outer T-cell zone of secondary lymphoid tissues, where
B cells interact with T cells. B cells then differentiate using 2 pathways: (1) a follicular pathway
that creates germinal centers and (2) an extrafollicular pathway. In the extrafollicular pathway
of both T-cell-dependent and -independent responses, B-cell precursors migrate to the splenic
bridging channel that connects the T-cell zone with the spleen red pulp or medullary cords in
the lymph nodes. They then differentiate into short-lived plasmocytes that produce low-affinity
antibody and form extrafollicular foci of such cells. In the follicular pathway , B-cell precursors of
germinal centers give birth to high-affinity memory B cells and long-lived plasmocytes. Germinal
centers of follicles, at least in tonsils, are composed of: (1) a dark zone with centroblasts (dividing
germinal-center B cells that undergo mutation of their immunoglobulin genes); (2) a light zone
with centrocytes (dark zone-exiting centroblasts), and follicular dendritic and T cells (with a large
proportion of CD4

and C δ genes encoding primary IgM and IgD with C γ ,C α ,orC

+ ,CD57 + T cells); (3) an outer zone with CD4 + ,CD57 − T cells; and (4) a

mantle zone with IgD T cells. The interaction with follicular helper

T cells supports selection of high-affinity centrocytes, leads to the differentiation into long-lived
plasmocytes and memory B cells, and stimulates centrocytes to recycle into centroblasts.
163 Receptor CXCR5 is a receptor for chemokine CXCL13, also named B-cell-attracting che-
mokine BCA1, a chemokine secreted by follicular stromal cells, T FH cells, and myeloid and
plasmacytoid dendritic cells.
164 T FH cells differ from type-1 (T H1 ) and -2 (T H2 ) helper T cells. Various lineages of helper T cells
have distinct differentiation pathways, such as CD4

+ resting B cells and CD4 +

+ +

,IL17 cells implicated in autoimmunity.