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B cells are mediators of the humoral response, or antibody-mediated immunity. By studying this particular cell group we learn more about the inner workings of the immune system, which consequently increases our awareness of the possible causes behind a variety of autoimmune disorders and cancers. Broad immunological research unlocks valuable insight of what future steps might be taken to treat these pathologies.
Development from stem cell to B cell
Generation of the B cell begins in the bone marrow where stem cells give rise to lymphoid cells. Throughout each stage of development the antibody locus— a site where an antigen interacts with the cell— undergoes genetic recombination. This recombination is specific to the developmental stage of the B cell. Development starts with the pro-B cell, which expresses Igα and Igβ. The cell matures further into the pre-B cell that expresses the pre-B cell receptor (Igμ) on its surface. Maturation in the bone marrow ends with the naïve B cell that expresses the B cell receptor (containing IgM and IgD) capable of recognizing an antigen. These cells then leave the bone marrow and enter the periphery (Cambier JC, et al. Nat Rev Immunol. 2007).
Subtypes of conventional B cells
Conventional B cells, also referred to as B-2 cells, terminally differentiate into one of two common subtypes upon activation:
Other B cell subtypes include:
Immunophenotyping of B cells through flow cytometry
Immature B cells express CD19, CD 20, CD34, CD38, and CD45R, but not IgM. For most mature B cells the key markers include IgM and CD19, a protein receptor for antigens (Kaminski DA. Front Immunol. 2012). Activated B cells express CD30, a regulator of apoptosis. Plasma B cells lose CD19 expression, but gain CD78, which is used to quantify these cells. Memory B cells can be immunophenotyped using CD20 and CD40 expression. The cells can be further categorized using CD80 and PDL-2 regardless of the type of immunoglobulin present on the cell surface (Zuccarino-Catania GV et al. Nat Immunol. 2014.). Globally, cytokines (such as interlukein-10) and chemokines involved with chemokine receptor 3 play an important role in transmitting the biological messages to drive the immune response.
A table of common B cell subtypes with some cell markers which can be useful for flow cytometry:
|B Cell Type||Marker||Cellular localization|
|B cell (all except plasma cell)||IgM, CD19||Secreted|
|Activated B cell||CD19, CD25, CD30||Secreted|
|Plasma cell||IgG, CD27, CD38, CD78, CD138, CD319||Secreted|
|Plasma cell||IL-6||Secreted (cytokine)|
|Plasma cell||CD138||Cell membrane|
|Memory cell||IgA, IgG, IgE, CD20, CD27, CD40, CD80, PDL-2||Secreted|
|Memory cell||CXCR3, CXCR4, CXCR5, CXCR6||Secreted (chemokines)|
|Marginal zone B cells||CD1, CD21, CD27||Secreted|
|Marginal zone B cells||Notch2||Cell membrane|
|Follicular B cells||IgD, CD21, CD22, CD23||Secreted|
|Regulatory B cells||IgD, CD1, CD5, CD21, CD24, TLR4||Secreted|
|Regulatory B cells||IL-10, TGFβ||Secreted (cytokines)|