Germinal center selection and the development of memory B and plasma cells

  title={Germinal center selection and the development of memory B and plasma cells},
  author={Mark J. Shlomchik and Florian J. Weisel},
  journal={Immunological Reviews},
Summary:  A hallmark of adaptive immune responses is the generation of long‐lived protection after primary exposure to a pathogen. In humoral responses, this protection stems from a combination of sustained antibody titers and long‐lived memory B cells (MBCs), with the former deriving from long‐lived plasma cells (PCs). Both types of cell are thought to primarily derive from the germinal center (GC), a unique structure that forms during the immune response to many types of antigenic stimuli… 

Regulation of germinal center B‐cell differentiation

Germinal centers are the main sites where antigen‐activated B‐cell clones expand and undergo immunoglobulin gene hypermutation and selection, and T‐helper cells in GC have been shown to have a central role in regulating B‐ cell selection by sensing the density of major histocompatibility complex (MHC):peptide antigen complexes.

Germinal-center development of memory B cells driven by IL-9 from follicular helper T cells

The GC development of memory B cells is promoted by TFH cell–derived IL-9, and deletion from T cells or from GC TFH cells led to impaired memory formation of B cells.

System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation

A system-level perspective of T cell-mediated GC B cell differentiation is presented, presenting and discussing the experimental and computational efforts on the regulation of the GCs and the areas where a Systems Biology approach may be useful to predict novel GCBC-T cell interaction dynamics.

Regulation of germinal center responses and B-cell memory by the chromatin modifier MOZ

Stage-specific deletion of monocytic leukemia zinc finger protein (MOZ), a histone acetyltransferase, is demonstrated that mutation of this chromatin modifier alters fate decisions in both primary and secondary responses, providing strong evidence that manipulating epigenetic modifiers can regulate fate decisions during humoral responses, and thus could be targeted for therapeutic intervention.

Regulation of the germinal center response by T follicular helper cells and type I interferons

This thesis defines how the GC response and Tfh cell differentiation are regulated by innate effectors, such as conventional dendritic cells (cDCs) and type I interferons (IFNs), in response to protein immunization adjuvanted by the dsRNA-analogue poly(I:C).

Regulated selection of germinal-center cells into the memory B cell compartment

An instructive model is proposed in which weak help from T cells maintains relatively high expression of Bach2, which predisposes GC cells to enter the memory pool.

Memory B Cells in Mouse Models

Memory B cells in mice are discussed, as defined by (1) cell surface markers; (2) multiple layers; (3) formation in a T cell–dependent and either GC‐dependent or GC‐independent manner; (4) formationIn a Tcell–independent fashion; and Lastly, the cells will touch upon in; (5) mouse models of autoimmune diseases.

T cell help to B cells: Cognate and atypical interactions in peripheral and intestinal lymphoid tissues

The cellular and molecular aspects of cognate T‐B interactions are described, and exceptional cases, especially those arising at intestinal lymphoid organs, at which T cells provide help to B cells in an atypical manner, independent of T cell specificity are highlighted.



Germinal-center-derived B-cell memory.

The inability to reliably identify memory B cells has hampered the study of memory B cell development and differentiation.

Plasticity and Heterogeneity in the Generation of Memory B Cells and Long-Lived Plasma Cells: The Influence of Germinal Center Interactions and Dynamics

Progress is reviewed on events in the germinal center, especially B–T interactions, which influence the development of memory and PC compartments and on Bmem cell heterogeneity that may underlie flexibility and self-renewal of long-lived humoral immunity.

Two waves of memory B-cell generation in the primary immune response.

The generation and long-term persistence of low-affinity IgG1 memory B cells and antibodies in ICOS-manipulated mice support the idea that low-AffinityMemory B cells may give rise to long- term antibody-forming cells.

Early appearance of germinal center–derived memory B cells and plasma cells in blood after primary immunization

The early stages of a primary immune response is examined, focusing on the appearance of antigen-specific B cells in blood, and finds no evidence for a blimp-1–expressing preplasma memory compartment, suggesting germinal center output is restricted to ASCs and B220+ memory B cells, and this is sufficient for the process of affinity maturation.

High affinity germinal center B cells are actively selected into the plasma cell compartment

This work describes a powerful new model that allows these processes to be followed as they occur in vivo, and shows how “quality control” over plasma cell differentiation is likely critical for establishing effective humoral immunity.

IL-21 regulates germinal center B cell differentiation and proliferation through a B cell–intrinsic mechanism

It is shown that the absence of IL-21 signaling profoundly affects the B cell response to protein antigen, reducing splenic and bone marrow plasma cell formation and GC persistence and function, influencing their proliferation, transition into memory B cells, and affinity maturation.

Imprinting the Fate of Antigen-Reactive B Cells through the Affinity of the B Cell Receptor1

A continuum of elementary to comprehensive humoral immune responses exists that is controlled by inherent BCR affinity, and lower affinity interactions show tempered GCs, producing Bmem and affinity-matured, long-lived PCs.

Transcriptional Profiling of Antigen-Dependent Murine B Cell Differentiation and Memory Formation1

It is suggested that humoral recall responses are more rapid than primary responses due to the expression of a unique transcriptional program by memory B cells that allows them to both be maintained at high frequencies and to detect and rapidly respond to antigenic re-exposure.

Aborted Germinal Center Reactions and B Cell Memory by Follicular T Cells Specific for a B Cell Receptor V Region Peptide

An immunoregulatory process is uncovered that restricts the memory pathway to B cells that communicate with CD4 T cells via exogenous foreign Ag.