Humoral immunity is one of the main arms of the adaptive immune response and protects live organisms from invading pathogens, including pandemic-causing viruses. The humoral immune response is mediated by antibodies secreted by plasma cells (PCs) that are newly formed in a primary response or differentiated from memory-B cells (MBCs) upon re-exposure to similar pathogens. In T-dependent immune responses, B cells are initially activated by signals generated through B cell antigen receptor engagement with antigen and by interaction with cognate T cells. Activated B cells participate in either germinal center (GC) or extrafollicular (EF) responses.
In EF responses, activated B cells rapidly proliferate and differentiate into unmutated MBCs or low-affinity antibody-secreting PCs, which are essential for early infection control before GC establishment. Conversely, GC responses produce high-affinity antibody-secreting PCs and MBCs, pivotal players in long-term immunity. GCs have two molecularly and functionally distinct zones, the dark zone (DZ) and the light zone (LZ). In the LZ, GC-B cells undergo positive selection that relies on cellular communication between GC-B cells and lymphoid/non-lymphoid cells, such as follicular helper T cells and follicular dendritic cells. Positive selection directs GC-B cells along one of three known B cell fates: PCs, MBCs, and DZ entering GC-B cells.
Activated B cells and positively selected GC-B cells rapidly change gene expression profiles to facilitate proliferation, migration, and differentiation. These biological processes are accompanied by metabolic reprogramming and controlled by multiple layers of regulatory mechanisms at the transcriptional and post-transcriptional levels. Malfunction of the complex regulatory machinery in GC-B cells can lead to the development of lymphoma, due to the accumulation of genetic and epigenetic alterations. With recent advances in massively parallel sequencing technology, a comprehensive picture of cell function has begun to reveal B cell biology and relationships between physiology and pathophysiology of GC-B cells.
This Research Topic aims to discuss current knowledge and future perspectives on molecular and cellular events for the functional output of GC and EF responses. We also wish to discuss B cells in GC-like, tertiary lymphoid structures forming in chronic inflammation as an extension of this research topic. We welcome the submission of Review, Mini-Review, Original Research, Hypothesis and Theory, Clinical Trial and Opinion articles that cover, but are not limited to, the following subjects:
- Genetic and epigenetic regulation of gene expression in GC/EF responses;
- Post-transcriptional regulation to control GC/EF responses
- Cellular function and metabolism governing GC/EF responses
- Molecular profiling and cellular dynamics of lymphoid and non-lymphoid cells in GC /EF responses: Spatial and temporal transcriptomics
- Signals and factors for the differentiation of B cells into MBCs and PCs in GC/EF responses
- Cell-to-cell communications between lymphoid/non-lymphoid cells and GC-B cells which lead to the flourish or decline of GC-B cells
- Novel methodologies and modeling to investigate molecular and cellular regulation of GC responses
- Deregulation of molecular programs in GC-B cells: transformation and lymphomagenesis
- Differentiation and functions of B cells within tertiary lymphoid structures (GC-like) in chronic inflammation: chronic infection, cancer, and autoimmune disease
Humoral immunity is one of the main arms of the adaptive immune response and protects live organisms from invading pathogens, including pandemic-causing viruses. The humoral immune response is mediated by antibodies secreted by plasma cells (PCs) that are newly formed in a primary response or differentiated from memory-B cells (MBCs) upon re-exposure to similar pathogens. In T-dependent immune responses, B cells are initially activated by signals generated through B cell antigen receptor engagement with antigen and by interaction with cognate T cells. Activated B cells participate in either germinal center (GC) or extrafollicular (EF) responses.
In EF responses, activated B cells rapidly proliferate and differentiate into unmutated MBCs or low-affinity antibody-secreting PCs, which are essential for early infection control before GC establishment. Conversely, GC responses produce high-affinity antibody-secreting PCs and MBCs, pivotal players in long-term immunity. GCs have two molecularly and functionally distinct zones, the dark zone (DZ) and the light zone (LZ). In the LZ, GC-B cells undergo positive selection that relies on cellular communication between GC-B cells and lymphoid/non-lymphoid cells, such as follicular helper T cells and follicular dendritic cells. Positive selection directs GC-B cells along one of three known B cell fates: PCs, MBCs, and DZ entering GC-B cells.
Activated B cells and positively selected GC-B cells rapidly change gene expression profiles to facilitate proliferation, migration, and differentiation. These biological processes are accompanied by metabolic reprogramming and controlled by multiple layers of regulatory mechanisms at the transcriptional and post-transcriptional levels. Malfunction of the complex regulatory machinery in GC-B cells can lead to the development of lymphoma, due to the accumulation of genetic and epigenetic alterations. With recent advances in massively parallel sequencing technology, a comprehensive picture of cell function has begun to reveal B cell biology and relationships between physiology and pathophysiology of GC-B cells.
This Research Topic aims to discuss current knowledge and future perspectives on molecular and cellular events for the functional output of GC and EF responses. We also wish to discuss B cells in GC-like, tertiary lymphoid structures forming in chronic inflammation as an extension of this research topic. We welcome the submission of Review, Mini-Review, Original Research, Hypothesis and Theory, Clinical Trial and Opinion articles that cover, but are not limited to, the following subjects:
- Genetic and epigenetic regulation of gene expression in GC/EF responses;
- Post-transcriptional regulation to control GC/EF responses
- Cellular function and metabolism governing GC/EF responses
- Molecular profiling and cellular dynamics of lymphoid and non-lymphoid cells in GC /EF responses: Spatial and temporal transcriptomics
- Signals and factors for the differentiation of B cells into MBCs and PCs in GC/EF responses
- Cell-to-cell communications between lymphoid/non-lymphoid cells and GC-B cells which lead to the flourish or decline of GC-B cells
- Novel methodologies and modeling to investigate molecular and cellular regulation of GC responses
- Deregulation of molecular programs in GC-B cells: transformation and lymphomagenesis
- Differentiation and functions of B cells within tertiary lymphoid structures (GC-like) in chronic inflammation: chronic infection, cancer, and autoimmune disease
