Compartments and Connections Within the Germinal Center

Abstract

Protective high affinity antibody responses emerge through an orchestrated developmental process that occurs in germinal centers (GCs). While GCs have been appreciated since 1930, a wealth of recent progress provides new insights into the molecular and cellular dynamics governing humoral immunity. In this review, we highlight advances that demonstrate that fundamental GC B cell function, selection, proliferation and SHM occur within distinct cell states. The resulting new model provides new opportunities to understand the evolution of immunity in infectious, autoimmune and neoplastic diseases.

NF-κB: blending metabolism, immunity, and inflammation

“…In fact, only B cells with increased antigen affinity are instructed to differentiate into long-lived antibody-secreting plasma cells (PCs) and memory B cells (MBCs). The GC requires a tight regulation to avoid hyper-responsiveness and autoimmunity [84]. In B cell follicles, B cells are supported by a specialized network of stromal cells named follicular dendritic cells (FDCs).…”

“…While part of the antigen-activated B-clones move to specialized areas in the lymph nodes where they differentiate into short-lived plasmablasts (PBs) secreting low-affinity antibodies, GC precursor B cells migrate into the center of the follicle to form an early GC. GC is divided in two distinct regions by day 7 after immunization: light zone (LZ) and dark zone (DZ) [84]. Within GCs, iterative rounds of mutation and selection occur via a cycle migration between the DZ where B cells undergo clonal expansion and SHM, and the LZ where positive selection occurs [16,83,84].…”

“…GC is divided in two distinct regions by day 7 after immunization: light zone (LZ) and dark zone (DZ) [84]. Within GCs, iterative rounds of mutation and selection occur via a cycle migration between the DZ where B cells undergo clonal expansion and SHM, and the LZ where positive selection occurs [16,83,84]. During positive selection, B cells capture antigen that is displayed on FDCs.…”

Classifying Germinal Center Derived Lymphomas—Navigate a Complex Transcriptional Landscape

“…Recent single-cell transcriptome studies provided a more detailed view, segregating the GC into more than the two morphologically distinguishable compartments [ 24 , 25 , 43 , 45 , 46 ]. Of note, two distinct B-cell populations have been described by Kennedy et al [ 25 , 47 ] in the DZ that differ both with respect to function and location: Proliferating DZ (DZp) cells transform into differentiating DZ (DZd) cells before they exit the DZ and re-enter the LZ ( Figure 2 b, [ 25 , 47 ]). Interestingly, gene signatures of the three compartments taken from [ 25 ] are found in/near spot areas F (LZ_up), D (DZp_up), and B (DZd_up) ( Figure 2 e and Figure A5 ), suggesting that our transcriptomic state space well recapitulates this tri-partition of the GC ( Figure 2 d).…”

Metabolic Program of Regulatory B Lymphocytes and Influence in the Control of Malignant and Autoimmune Situations

“…Among the specialized cells of the adaptive immune system, B lymphocytes play a pivotal role for the detection of danger signal and the presentation of antigen to T cells to mount efficient germinal center (GC) responses ( 1 , 2 ). Following activation signals subsequent to a fine dialogue with the T cells, B cells acquire effector and regulatory functions leading to the production of antibodies and the secretion of cytokines, and thus develop humoral immune responses for antigen neutralization and participate to the control of the cellular immune responses ( 3 , 4 ).…”