Lecture 5: B Cell Development and Generation of Primary Antibody Repertoire Flashcards
Heavy chain of antibodies is encoded by ____ different gene segments as opposed to the variable region which is encoded by ___.
3; 2
A single plasma cell makes ____ kind of antibody while a B cell can deviate and make 2 or more heavy chain isotypes
1
What is the next stage of a B cell after stem cell?
ProB
What kind of rearranging is present in ProB cells?
IgH DJ (no light chain rearrangements)
What is the earliest cell type that synthesizes a detectable Ig gene product?
PreB cells
What is the hallmark of the next stage, immature B cells?
kappa and lambda light chains that associate with mu heavy chains and the assembled IgM molecules are expressed on the cell surface
Describe mature B cells
they have acquired a complete Ig and have antigen specificity so they migrate out of the bone marrow
Mature B cells coexpress which two heavy chains?
mu and delta
True or false: Mature B cells IgM and IgD each have the same V region and therefore the same antigen specificity?
TRUE
Define allelic exclusion
the expression of only one allele in a cell
How many varieties of V gene regions are there? D? J?
V: 50-100
D: 20-30
J: 5-6
What stretches of DNA mediate VDJ recombination?
recognition sequences (RSS) - stretch of 7-8 nucleotides flanking D and on 3’ end of V and 5’ end of J
What enzymes recognize RSS?
RAG1 and RAG2 (recognize two RSS and cleave DNA between exon and RSS)
What is the name of the excised portion of VDJ rearrangements?
BREC
How is the secreted vs. membrane IgM produced?
alternative splicing
How do B cells express both mu and delta heavy chains?
alternative splicing of C region (same VDJs though)
What is N-region addition and how does it contribute to antibody diversity?
the addition of new nucleotides to the VDJ genes during rearrangement (accomplished by deoxyribonucleotide transferase)
What is B cell tolerance?
selection and removal of B lineage cells in the bone marrow that have non-functional VDJ rearrangements of express self-reactive antibody
What are the 3 routes of removal for antibodies with self reactivity?
1) become anergic
2) deleted
3) rescued by receptor editing
When is the V gene selected in recombination?
as a late ProB cell
When is heavy chain rearrangement turned off?
when IgM goes to the surface of the cell (mu heavy chain binds to surrogate light chain that takes the molecule to the surface)
What are 3 features that lead to a large antibody repertoire?
1) combinatorial V(D)J gene joining
2) N nucleotide addition by TdT
3) Combinatorial association of H and L chains
What are TCRs?
T Cell Antigen Receptors (structurally similar to Ig in that they have analogous variable and constant regions)
What are the majority of TCRs?
ab
The V regions of alpha and gamma chains are encoded by ___ and ____ gene segments
V and J
True or false: TCR genes rearrange by the same mechanism as Ig genes
TRUE
True or false: each T cell expresses a single TCR specific for one particular antigenic determinant?
TRUE
What 3 gene families encode IgG?
1) heavy chain
2) kappa
3) lambda
What is a myeloma?
1 B cell becoming cancerous
True or False: in pre-B cells, both heavy and light chain genes are rearranged
FALSE; light chains are still in their germline state - do not rearrange until immature B cell
How does allelic exclusion work?
VDJh rearrangement on one allele; VJ(L) rearrangement on the other allele
