Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
32 Cards in this Set
- Front
- Back
|
What are the four phases of B cell development? And where do they occur?
|
- Phase I: Generation of B cells in the bone marrow = bone marrow
- Phase 2: Elimination of self-reactive B cells = bone marrow - Phase 3: Migration of mature B cells to the periphery = blood - Phase 4: Terminal antigen-stimulated differentiation of B cells into memory cells and plasma cells = lymph node, spleen, peyer's patches |
|
|
How are BCR and secreted Ig of a B cell related?
|
- The BCR and secreted Ig of a B cell have the same specificity
|
|
|
What are the two ptns associated with membrane bound Ig (B cell receptor)?
How are these two ptns linked? function? |
- Ig-alpha and Ig-beta
- disulfide-linked - intracellular signaling |
|
|
What is the property of amino-terminal regions of the heavy and light chains?
What is this region called? |
- they are variable in sequence from one IgG molecule to another, generating diversity
- variable region |
|
|
What is MOA of origins of variable region diversity of IgG?
What is the term when Gene segments rearrange to form a functional gene? |
Variable region of immunoglobulin gene is in a segmented form along a chromosome that cannot be expressed -> each segment encodes an alternative version of part of the variable region -> Gene segments rearranged in different combinations to generate diversity
- somatic recombination |
|
|
What are the 2 families of gene segments that combine to form the human variable region of k light chain locus?
What is the constant region encoded by? |
- variable (V) gene segments and joining (J) gene segments
- C gene segment |
|
|
What is MOA of somatic recombination of the light chain locus?
|
- Light chain V region genes are constructed from two segments: a variable (V) and a joining (J) gene segment in genomic DNA are joined to form a complete light chain V region exon -> after rearrangement, the light chain gene consists of three exons, encoding the leader (L) peptide, V region and C region, that are separated by introns
|
|
|
What is MOA of the somatic recombination of the heavy chain locus?
|
- diversity (D) and J gene segments join -> V gene segment joins to the combined DJ sequence -> form complete heavy chain V region exon
|
|
|
MOA of gene rearrangement of the type occuring in Ig and T cell receptor genes?
|
- Rearrangement achieved by cut and paste in which the intervening DNA is removed as a circle -> different combos of different segments are brought together
|
|
|
What is germline organization of human heavy chain locus?
|
- 3 families of gene segments contribute to variable region – variable (V) gene segments, diversity (D) gene segments and joining (J) gene segments -> these three diff segments combine to form variable region, with a separate constant region encoded by C gene segment
|
|
|
What are the two functions of the V(D)J recombinase (an enzyme)?
|
- Enzymes of DNA recombination and repair found in all cells (DNA ligase IV, Terminal deoxynucleotidyl transferase (TdT))
- Lymphocyte-specific components (Recombination activating genes (RAG-1 and RAG-2) form RAG complex) |
|
|
MOA of recombination machinery btwn V and J segment of light chain gene?
What process occurs for the coding joint to form? |
- a RAG complex binds to the 23 bpspacer and another to the 12 bp spacer -> recombination signal sequence (RSS) containing a 12 bp spacer is brought together with that containing a 23 bp spacer (aka 12/23 rule: ensures that gene segments are joined in the correct order) -> DNA molecules are broken at the ends of the heptamer sequences -> joined together with diff topologies -> excision of the region of dna that was originally btwn the V and J segments to be joined -> within the chromosomal dna, the V and J segments are joined to form the coding joint
- involves opening up of hairpins that were formed at the original point of cleavage at one end of each V and J segment -> repairing of these ends and the DNA in a way that introduces additional variability into the nucleotide sequence around the joint. |
|
|
How is junctional diversity generated during gene rearrangement to form coding joint?
|
- RAG complex binds to and cleaves recombination signal sequences -> develop hairpin -> RAG-mediated cleavage of hairpin -> generates palindromic P-nucleotides -> N-nucleotide additions by TdT -> pairing of strands -> unpaired nucleotides are removed by an exonuclease -> these gaps are filled by DNA synthesis and ligation to form coding joint
|
|
|
What is the order of gene rearrangements leading to the expression of cell-surface Ig?
What happens if rearrangement is unproductive? What if that is also unproductive? |
- heavy chain genes are rearranged before the light chain genes
- rearrangement is attempted on the second chromosome - apoptosis occurs |
|
|
What is the process of maturation of B cell?
What Ig gene rearrangement occurs in early pro-B cell? in Large pre-B cell? in immature B cell? In mature B cell? |
- early pro-B cell -> large pre-B cell -> immature B cell -> mature B cell
- V-DJ rearrangement - completion of heavy chain gene arrangement, mu heavy chains are synthesized and assembled into a complex with surrogate light chain and with Ig-alpha and Ig-beta, proceed to light chain gene rearrangement - completion of a productive light chain gene rearrangement and assembles with mu to form IgM, transported to cell surface. - IgD and IgM is on the surface |
|
|
How does the Pre-B cell receptor differ from the B cell receptor?
|
- Pre B cell receptor has a surrogate light chain (VpreB and lamda5) instead of a light chain
|
|
|
What is allelic exclusion?
What does this signal? |
- Inhibition of heavy chain recombination of pre-B cell receptor
- Signals initiation of k light chain recombination |
|
|
What is CD19?
|
- gene that encodes a cell surface co-receptor which assembles with the antigen receptor of B lymphocytes in order to decrease the threshold for antigen receptor-dependent stimulation
|
|
|
How are different immunoglobulin isotypes formed?
|
Different heavy chain C regions are encoded by different C gene segments in the heavy chain locus
|
|
|
How is there a co-expression of IgM and IgD on B cells?
MOA? |
- by differential RNA splicing
- cleavage and polyadenylation at the mu site and splicing btwn Cmu exons yields mRNA encoding mu heavy chain (IgM) -> cleavage and poyadenylation at the delta site -> different pattern of splicing that removes Cdelta exons yields mRNA encoding delta heavy chain |
|
|
What are the first isotypes expressed?
When are they expressed? Expressed by? |
- IgM and IgD are first isotypes to be expressed
- Expressed before encounter with antigen - Expressed by mature naïve B cells |
|
|
What are the only two isotypes that can be expressed simultaneously by same B cell?
How? |
- IgM and IgD
- Accomplished by differential splicing of primary RNA transcript |
|
|
Are bone marrow stromal cells lymphoid or non-lymphoid?
Function? |
- non-lymphoid
- Provide microenvironment for B cell development & Make cell-cell contact with developing B cells (by cell adhesion molecules) & Produce growth factors for B cell development (Stem cell factor (SCF) &)Interleukin-7 (IL-7) |
|
|
What is screen in immature B cells before release to circulation?
What happens to autoreactive B cells? |
- purged of self-reactive cells
- Eliminated by clonal deletion of multivalent antigen or Inactivated (anergy) of soluble antigen |
|
|
What is the circulation pathway of B cells through lymph nodes?
|
- Enter the cortex through high endothelial venules -> Congregate in primary lymphoid follicles -> Interact with follicular dendritic cells (FDCs) -> Receive survival signals -> Leave node in efferent lymphatic vessel -> Return to blood stream at subclavian vein -> Most mature naïve B cells die after few days
|
|
|
How do B cells circulate through lymph nodes when they do not encounter their specific antigen?
|
- leave blood and enter cortex of lymph node through specialized high endothelial venules (HEV) -> the B cells pass through primary follicles and leave the node in efferent lymph, which eventually joins blood at veins in neck
|
|
|
What happens when B cells do encounter antigen in secondary lymphoid tissues? What happens in the germinal center?
|
- B cell enter lymph node thru HEV encounters antigen in lymph node cortex -> B cell is activated by CD4 helper T cells in Tcell areas -> formprimary focus of dividing cells -> some B cells migrate directly to medullary cords and differentiate into plasma cells or migrate into primary follicle to form germinal centers - B cells continue to divide and differentiate -> activated B cells migrate to medulla of lymph node or to bone marrow to complete their differentiation into plasma cells
|
|
|
What are the three zones recognized in a lymphoid follicle?
|
- Mantle zone of resting B cells, dark zone of proliferating blasts, light zone of differentiating cells What is present btwn follicles? - T cells, interdigitating cells (antigen-presenting), BV, and sinuses
|
|
|
How do production of transmembrane IgM differ from secreted IgM?
|
- by differential processing of heavy chain mRNA
|
|
|
What is class switching?
How is expression of IgG, IgA and IgE accomplished? What signal is required for this to occur? |
- Isotype switching to express IgG, IgA and IgE, where Ig produced have different C regions but identical antigen specificities
- by somatic recombination within C gene cluster of the heavy chain locus - Requires signals from T helper cells |
|
|
How does Ig isotype switching occur?
|
- IgM and IgD produced -> looping out and switch region recombination -> specific isotype produced
|
|
|
Where does isotype switching occur?
|
- in germinal centers
|
