Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 160

3.12.5 Main Regulators of B-Cell Proliferation in Germinal

Centers

Transcription factors myeloblastosis viral oncogene homolog MyB and forkhead
box FoxM1 are synergistic master regulators of B-cell proliferation in germinal
centers, where antigen-stimulated B cells highly proliferate, undergo somatic
hypermutation of immunoglobulin genes and are selected according to synthesized
high-affinity antibodies [ 290 ]. Germinal center-resident B cells, or centroblasts,
derive from naive B cells, from which they differ due to the activation of genetic
programs that control cell proliferation, such as Aurora kinase-A and budding
uninhibited by benzimidazoles homolog BuB1 (a.k.a. mitotic checkpoint kinase

MAD3L and BUBR1), and pro-apoptotic programs and repress anti-apoptotic, cell
cycle arrest, DNA repair, and those that regulate signal transduction primed by
cytokines and chemokines.

β

3.12.6 B Cell-T Cell Interactions

CD4 T cells participate in humoral immunity, as they help B cells, and enhance

cellular immunity by producing cytokines. Conversely, effector and regulatory
B cells not only intervene in humoral immunity against pathogens and autoantigens,
but also regulate CD4

+

T-cell responses.
Antibody production by B cells to protect against many pathogens is the B-cell's
most important effector function. However, effector and regulatory B-cell subsets
can enhance effector and memory CD4

+

T-cell responses, independently of anti-
body production, as they regulate the development, proliferation, and maintenance
of these CD4

+

T cells. They indeed yield costimulation and produce inflammatory
and polarizing cytokines that direct the proliferation and effector functions of
responding T cells, in addition to antigen presentation [ 291 ]. B cells optimize
proliferation of CD4

+

T cells and can enforce or stabilize the differentiation of
T cells into polarized effector cell subsets in cooperation with dendritic cells. B cells
promote the development of CD4

+

+ T-cell memory and intervene in the reactivation

of memory CD4 T cells.

Moreover, B cells may also attenuate immune responses, as they can improve
the development, survival, and proliferation of regulatory T cells [ 291 ]. In addition,
IL10-producing regulatory B cells can suppress effector T-cell responses.

+

3.12.7 Plasmocytes

Plasmocytes (size m), or plasma cells (plasma B cells), are effector B cells

located in the bone marrow and lymphoid organs. Plasmocytes can survive for long
periods in survival niches in secondary lymphoid organs, bone marrow, or inflamed
tissue [ 292 ].

∼ 13