Lecture 7: B Cell Development Flashcards
What is the sole function of a plasma cell?
Secrete antibodies
what does it mean to have a fully differentiated cell?
Cannot differentiate any further
A blood stem cell can differentiate into two cells. What are these?
- Myeloid stem cell
- Lymphoid stem cell
A myeloid stem cell can differentiate into three cell types:
- Red blood cells
- Platelets
- Myeloblast
A myeloblast can differentiate into granulocytes. What are the three granulocytes?
- Eosinophil
- Neutrophil
- Basophil
A lymphoid stem cell can further differentiate into
Lymphoblast
A lymphoblast can differentiate into:
- B lymphocyte- Plasma cell
- T lymphocyte
- Natural killer cell
Granulocytes (Eosinophil, Neutrophil, Basophil), Plasma cell, T lymphocyte, Natural killer cell are all
White blood cells
Stages of B Cell development
- B cells develop from pluripotent stem cells in the bone marrow.
- The stem cell develops into a mature IgM+ B cell.
- The mature, naive B cells circulates through the peripheral lymphoid organs.
- B cells that fail to encounter antigen die through apoptosis.
- B cells that encounter antigen (1st signal) and receive a second signal are activated.
B Lymphocytes are predicted to generate approximately 1x10^11 distinct antigen receptors.
However, the human genome only contains about 25,000 distinct genes.
How does such a limited genome enable the generation of an almost infinite number of antigen receptors?
Germline organization of a gene
Explain the germline organization of a typical gene
- In a genomic DNA, there is a promoter and various types of exons (ex: exon 1 and exon 2).
- Transcription happens and it’s gonna result in a primary transcript (has both exons 1 and 2).
- Splicing results in formation of mRNA
- Translation combines both exons 1 and 2 and forms a protein.
What happens in the diversity by V(D) J Somatic Recombination?
- V, D, and J gene segments are in tandem.
- In a single lymphocyte clone, one D gene segment randomly recombines with one J gene segment.
- A V gene segment then recombines with the D-J segment, generating a recombined V-D-J gene.
- The new gene is then transcribed. The V-D-J gene segment is spliced to the first C region (μ Chain).
- The resulting mRNA is translated to generate a unique IgM heavy chain.
The germline organization of antigen receptor gene loci
- The Ig heavy chain locus contains variable (C) region gene segments.
- The variable region gene segments are followed by diversity (D) and joining (J) gene segments.
- VDJ segments are followed by sequentially arranged constant gene segments.
- The light chain loci displays a similar organization to the heavy chain locus, except it lacks any D gene segments. There are two light chain loci - κ and λ
Each gene recombination generates a unique ______ region. - unique antigen specificity.
variable
The _______ region, does not change- conserved effector function.
constant
What are sources of diversity?
- number of V gene segments.
- number of diversity (D) gene segments.
- number of joining (J) gene segments.
Stages of B cell activation
(starts with Naive B cell encounters antigen)
- Naive B cell encounters antigen.
- Helper T cells stimulate B cells.
- Activated B cells begin clonal expansion.
- Some B cells differentiate into antibody secreting plasma cells.
- Others (some daughter cells) become memory cells.
- Others switch class to produce a new Ig isotype.
Memory Lymphocytes
- produced from naive lymphocytes as a result of antigen exposure.
- persist for years in an inactive state. Rapidly reactivated by repeat exposure to antigen and mediate faster, more potent immune responses.
- some active lymphocytes differentiate into memory lymphocytes.
Secondary vs. Primary Antibody Responses
- Secondary responses are more effective at dealing with infections.
Primary response:
Lag after immunization: usually 5-10 days
Peak response: smaller
Antibody isotype: usually IgM>IgG
Antibody affinity: lower average affinity, more variable.
Secondary response:
Lag after immunization: usually 1-3 days
Peak response: larger
Antibody isotype: Relative increase in IgG and, under certain situations, in IgA or IgE (heavy chain class switching)
Antibody affinity: higher average affinity (affinity maturation)
Class Switching
changing of an antibodies constant region.
A clone of B cells is not committed to make a single Ig isotype forever.
Does not affect the variable region.
- Cytokine induce rearrangements at the heavy chain locus.
- Exposed DNA ends are joined together.
- End result: New class of Ig (ex: IgG)
- DNA encoding some constant regions is deleted.
Role of cytokine signals in class switching
induce rearrangements at the heavy chain locus.
In class switching, the antibody retains antigen specificity. However,
new constant region = new effector functions.
