Exam 2 Lecture 10: B Cell Development Flashcards
Phases of B cell development and where they occur
Repertoire assembly: generate B-cell receptors in bone marrow
Negative selection: Fix B-cell receptors that bind to components on human body
Positive selection: immature B-cells become mature B-cells in secondary lymphoid organs
Searching for infection: recirculation of mature B-cells between lymph, blood, 2ndary lymphoid tissues
Finding infection: Activation and clonal expansion of B-cells by pathogen derived antigens in 2ndary lymphoid tissues
Attacking infection: Differentiation to antibody secreting plasma cells and memory B-cells in 2ndary lymphoid tissues
What part of B-cell development occurs in the bone marrow
Generate a functional receptor
Stem cell > Pro-B cell > (checkpoint 1) > Pre-B cell > (checkpoint 2) > immature B cell
What part of B-cell development occurs in secondary lymphoid organs
negative selection (central & peripheral tolerance) > immature B cell > positive selection > mature naive B cell > primary follicle B cell > memory B cell and plasma cell
How many chances do B cells have to rearrange their heavy chains? Light chains?
Heavy chain: 2 chances
D-J rearrangement on both chromosomes
V-DJ rearrangement on 1st chromosome
(if unsuccessful) >
V-DJ rearrangement on 2nd chromosome
Light chain: 4 chances
κ gene on 1st chromosome > κ on 1st chromosome > λ on 1st chromosome > λ on 2nd chromosome
What are the two checkpoints that immature B cells encounter during development in the bone marrow
Checkpoint #1: pre-BCR (consists of rearranged heavy chain & surrogate light chain) selects for functional heavy chains
Checkpoint #2: BCR full heavy and light chain, can properly signal
What happens to cells that don’t properly rearrange their receptors?
Die by apoptosis
What signals do bone marrow stromal cells provide to maturing B cells
- Make specific contacts with development B-cells through adhesion (prevent leaving) (VCAM-1)
- Produce growth factors that support B-cell survival (IL-7)
How is the rearrangement of immunoglobulin loci restricted to only B cells
Pax5 transcription factor only expressed on B cells, supports rearrangement and transcription
Binds to DNA and allows RAG enzymes to enter
In negative selection, what are central and peripheral tolerance for B cells
Central tolerance: arrest of self-reactive B-cells in the bone marrow
Undergoes receptor editing
Peripheral tolerance: arrest of self-reactive B-cells outside of the bone marrow
Undergoes anergy and becomes unresponsive
In negative selection, what is receptor editing
If a B-cell is self-reactive in the bone marrow, the cell rearranges its light chains until it is not self-reactive and can leave cell (or apoptosis)
In positive selection, which cell type in the B cell follicles provide signals for B cells to transition from immature to mature naive B cells?
Follicular dendritic cells
What changes occur to B cells when they mature
Immature: high IgM, low IgD
Mature: low IgM, high IgD
What two events need to happen for mature naive B cells to survive and proliferate
Encounter it’s antigen
Encounter T cell activated by same antigen
What two locations do mature activated B cells go to and what do they differentiate into
Medullary cords: short-lived plasma cells secreting IgM
Germinal center: isotype switching, somatic hypermutation to become long lived plasma cells and memory B cells
How are B1 cells different from conventional B cells
Express CD5, produces starting prior to birth, Igs have minimal diversity, mostly IgM, mostly located in periphery and self-renew there, antibody production doesn’t change over time
Provide protection short term until B2 cells can be effective
