Type I cytokine profiles of human naïve and memory B lymphocytes: a potential for memory cells to impact polarization
Alenka Gagro1, Drazen Servis, Alma-Martina Cepika
1Institute of Immunology, Zagreb, Croatia. agagro@imz.hr
Insights
Human B cells, both naive and memory, can respond to type 1 polarizing environments. Memory B cells, however, can promote and amplify type 1 immune responses, influencing T-helper cell differentiation.
Area of Science:
- Immunology
- Cell Biology
- Cytokine Signaling
Background:
- B cells differentiate into type 1 or type 2 pathways, influencing immune responses.
- Understanding the role of naive and memory B cells in type 1 responses is crucial for immune modulation.
Purpose of the Study:
- To compare the capacity of human naive and memory B cells in type 1 polarizing responses.
- To investigate the expression of key receptors and cytokines involved in type 1 immunity by B cells.
Main Methods:
- Flow cytometry to analyze receptor expression (IL-12Rbeta1, IL-12Rbeta2, WSX-1).
- Stimulation assays involving B-cell receptor (BCR) engagement, CD154, and interferon-gamma (IFN-gamma).
- Measurement of cytokine production (IL-12 p70, IL-12 p40, IL-23 p19) and assessment of T-helper cell polarization.
Main Results:
- BCR engagement was the primary signal for IL-12Rbeta1 expression, potentiated by CD154/IFN-gamma and inhibited by IL-12.
- IL-12Rbeta2 was induced on a minority of B cells by IFN-gamma alone or with other signals.
- Memory B cells, unlike naive B cells, produced IL-12 p40 and IL-23 p19 and promoted IFN-gamma synthesis in T-helper cells.
Conclusions:
- Both naive and memory B cells can respond to type 1 polarizing environments.
- Memory B cells play a significant role in maintaining and amplifying type 1 immune responses through T-dependent signaling.
- B cells, particularly the memory subset, contribute to the direction and strength of type 1 immunity.
Abstract:
B cells bifurcating along 'type 1' or 'type 2' pathways under the influence of polarizing cytokines can, in turn, influence the direction of an immune response. Here, we compare the capacity of human B cells residing within naïve and memory compartments to participate in type 1 polarizing responses. B-cell receptor (BCR) engagement provided the main signal for interleukin (IL)-12Rbeta1 expression in the two subsets: this was potentiated by CD154 together with interferon-gamma (IFN-gamma) but inhibited by IL-12. IL-12Rbeta2 could be induced on a minority of B cells by the same signals, and also by IFN-gamma alone. WSX-1, a receptor for IL-27, was expressed in both subsets with no evidence for its regulation by the signals studied. While neither subset was capable of secreting much IL-12 p70, memory B cells could produce a small amount of IL-12 p40 on CD40 ligation. Memory B cells also, exclusively, expressed IL-23 p19 mRNA on BCR triggering. Importantly, products of appropriately stimulated memory--but not naive--B cells were shown to promote the synthesis of IFN-gamma in uncommitted T-helper cells. The data indicate an equal capacity for naïve and memory B cells to respond within a type 1 polarizing environment. Although poorly equipped for initiating type 1 responses, B cells--by virtue of the memory subset--reveal a capacity for their maintenance and amplification following T-dependent signalling.
Related Concept Videos
01:23Cells of the Adaptive Immune Response
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
01:24B Cell Activation and Differentiation
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:23Immunological Memory
What is Immunological Memory?
Immunological memory is an integral function of the immune system that allows it to recognize and react more rapidly and effectively to pathogens previously encountered. This feature is...
01:20Special Features of Adaptive Immunity
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...