CD27 is acquired by primed B cells at the centroblast stage and promotes germinal center formation
Yanling Xiao1, Jenny Hendriks, Petra Langerak
1Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Insights
CD27 expression on mouse B cells is crucial for germinal center formation and B cell expansion during immune responses. Its absence delays germinal center development but does not impact antibody production or somatic hypermutation.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD27 is a key marker and mediator in human B cell responses.
- Its role in mouse B cell immunity requires further elucidation.
Purpose of the Study:
- To investigate CD27 expression and function on mouse B cells.
- To determine the role of CD27/CD70 interactions in B cell responses and germinal center formation.
Main Methods:
- Analysis of CD27 expression during B cell differentiation.
- Utilizing CD27 knockout mice to study immune responses to influenza virus.
- Adoptive transfer experiments in CD27/CD28 double knockout mice.
Main Results:
- CD27 is acquired at the centroblast stage and lost upon differentiation, not marking somatically mutated B cells.
- Germinal center formation was delayed in CD27 knockout mice following influenza infection.
- CD27 deficiency did not alter somatic hypermutation or antibody production (IgM, IgG, IgA).
- CD27 promotes germinal center formation and IgG production via B cell stimulation and by T cells partially substituting for CD28.
Conclusions:
- CD27 plays a significant role in germinal center formation and B cell expansion in mice.
- CD27 influences immune responses through distinct mechanisms involving both B and T cells.
Abstract:
Studies on human B cells have featured CD27 as a marker and mediator of the B cell response. We have studied CD27 expression and function on B cells in the mouse. We find that B cells acquire CD27 at the centroblast stage and lose it progressively upon further differentiation. It is not a marker for somatically mutated B cells and is present at very low frequency on memory B cells. Enrichment of CD27 among centroblasts and the presence of its ligand CD70 on occasional T and B cells in or near germinal centers (GCs) suggested a role for CD27/CD70 interactions in clonal B cell expansion. Accordingly, GC formation in response to influenza virus infection was delayed in CD27 knockout mice. CD27 deficiency did not affect somatic hypermutation or serum levels of virus-specific IgM, IgG, and IgA attained in primary and recall responses. Adoptive transfer of T and B cells into CD27/CD28(-/-) mice revealed that CD27 promotes GC formation and consequent IgG production by two distinct mechanisms. Stimulation of CD27 on B cells by CD28(+) Th cells accelerates GC formation, most likely by promoting centroblast expansion. In addition, CD27 on T cells can partially substitute for CD28 in supporting GC formation.
Related Concept Videos
01:40Cell-mediated Immune Responses
01:23Cells of the Adaptive Immune Response
01:28Diversity of Antigen Receptors
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
01:22Antigen Presenting Cells
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
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...