Lecture 2 - B cells Flashcards
Development and activation of B cells
- The development of B-cells begins in the bone marrow and is driven by IL-7 produced by marrow stromal cells.
- Cells are activated by encountering their cognate antigen
- Activated B cells secrete antibodies
- Activated B-cells develop into long-lived plasma and memory cells which persist in lymph nodes or return to the bone marrow
Precursors of B1 and B2 cells
- Fetal liver–derived HSCs are the precursors of B-1 cells.
- These respond to T-independent antigens and make natural antibodies reactive with polysaccharides.
- Bone marrow–derived HSCs give rise to the majority of B cells (B-2).
- These cells develop into marginal zone B cells or into follicular B cells
Stem cell (development and response to antigen)
Anatomic site: Bone marrow
Ig DNA, RNA: Unrecombined/germline DNA
Ig expression: None
Surface markers: CD43+
Response to antigen: None
Pro-B cell (development and response to antigen)
Anatomic site: Bone marrow
Ig DNA, RNA: Unrecombined/germline DNA
Ig expression: None
Surface markers: CD43+, CD19+, CD10+
Response to antigen: None
Pre-B cell (development and response to antigen)
Anatomic site: Bone marrow
Ig DNA, RNA: Recombined H chain gene (VDJ); u mRNA
Ig expression: Cytoplasmic u and pre B-receptor associated u
Surface markers: B220lo, CD43+
Response to antigen: None
Immature B cell (development and response to antigen)
Anatomic site: Periphery
Ig DNA, RNA: Recombined H chain gene (VDJ), k or λ chain genes, u or k or λ mRNA
Ig expression: Membrane IgM (u + k or λ light chain)
Surface markers: IgMlo, CD43-
Response to antigen: Negative selection (depletion), receptor editing
Mature B cell (development and response to antigen)
Anatomic site: Periphery
Ig DNA, RNA: Alternative splicing of VDJ-C RNA (primary transcript) to form Cu and Cδ mRNA
Ig expression: Membrane IgM and IgD
Surface markers: IgMhi
Response to antigen: Activation (proliferation and differentiation)
Functional changes after B cell activation
- Clonal expansion
- Antibody secretion
- Isotype switching
- Affinity maturation
- Memory B cells forming
Role of heavy chains in antibodies
- Regulate the formation of pentamers (IgM) and dimers (IgA)
- Determine binding to cells via Fc receptors.
- Determine functional properties (eg: C’ fixation )
Role of light chains in antibodies
- Important for antigen specificity and binding
- labelled as either k or λ
Weight of heavy and light chains
Heavy chain: 50kDa
Light chain: 25 kDa
Full Ig: 150kDa
Role of IgA
- Found of mucosal surfaces and in many bodily secretions
- Important first line of defence against antigens
- about 13% of total serum
- are usually monomers or dimer structures
Role of IgG
- Important for memory/ long term immune response
- Binds many pathogens to control infections
- about 80% of total serum
- monomer structure
Role of IgM
- Important for initial response to a pathogen/infection (short term immune response
- controls B cell activation
- about 6% of total serum
- pentamer structure
Role of IgE
- Important for allergic responses and responding to intestinal parasites
- less than 0.1% of total serum
- monomer structure