Chapter 6 - B cell development (Exam 3) Flashcards
B cells develop in the
bone marrow
B cells are activated in the
secondary lymph tissues
B cells migrate from
bone marrow –> blood –> secondary lymph tissues
Function of B cells
Make immunoglobulin
Negative selection of B cells occurs in
bone marrow
Positive selection of B cells occurs in
Secondary lymphoid tissues
1st identifiable cell of B cell lineage
Pro-B cell
Anti-CD34
Isolate development of B cells
Rearrangement of heavy-chain genes begins where
in pro-b cell
CD molecules
Cluster of differentiation
Define developmental stage and properties of cells
Where mu heavy chain is made
Large pre-B cell
1st checkpoint
Pro B cells
Rearrangement of heavy-chain genes
2nd checkpoint
Pre B cells
Rearrangement of light-chain genes
Stroma
Supportive cells and connective tissue in any organ
Lymphoid Stromal cells provide
contact-mediated signaling
soluble growth factors (IL-7)
Heavy chain rearrangement is inefficient and imprecise in
Pro-B cells
Nonproductive rearrangement
P and N nucleotide insertion no longer codes for Ig
Productive rearrangement
P and N nucleotide insertion codes for Ig
Apoptosis in B cells occurs when
V-DJ rearrangement does not occur on either allele
Allelic Exclusion
Only one allele for each heavy and light chain
Ensures single antigen specificity
(monoclonal antibody)
Allelic exclusion at heavy chain gene
1 heavy chain with one light chain
Without allelic exclusion at heavy chain gene
2 different heavy chains and 1 light chain
You will die
Formation of Pre-B cell receptor signals
Successful heavy chain rearrangement
Surrogate light chain
Signals pro B to pre B cell
Functions of Pre-B cell receptors
Eliminates pro-B without functional mu heavy chain
Prevents Ig from having more than 1 heavy chain
Allelic exclusion in pre-b cell receptors
Stop RAG genes
degrade RAG proteins
Stabilize Ig gene arrangement
After expansion of pre b cells
Make ~85 pre b cells with same heavy chain but different light chain
Rearrangement of light chains
Allelic exclusion
Isotype exclusion (k or l)
When complete Ig is at surface
Signals to stop light-chain rearrangement and proliferate
Pax5
binds to B cell promoters; defines B
Required for activation of genes for rearrangement of Ig genes
B cells ONLY
Negative selection
against B cells that recognize self
Non self reactive B cells
alternative splicing will make IgD and IgM then B cell leaves bone marrow
Mechanisms of B cell tolerance
Central tolerance (in BM)
Peripheral tolerance (out BM)
In ALL immature B cells, ____ of any antigen to receptor causes ______.
binding
apoptosis/inactivation
Central tolerance
Receptor editing
Anergy
Receptor Editing
Repeatedly rearrange light chains and test for self-reactivity
Self tolerant B cell
Leaves BM and goes to secondary lymphoid tissue to mature
Clonal deletion
selective death of developing lymphocyte
Anergy
developmental arrest where B cell makes IgM and IgD but IgM is nonfunctional and retained inside cell
Cell enters periphery but dies after 1-5 days
Central and peripheral tolerance do not remove
B cells reactive to inaccessible self antigens
Autoimmune response
Self-antigens accessible to binding surface IgM
Postive selection
Non-self antigen in B cell follicles of secondary lymphoid tissue promotes B cell survival
B cells home to lymph node from blood through
HEV
high endothelial venule
B cells compete for access to follicles
Follicular dendritic cells
B cell must interact to mature
Mature B cells remain in
circulation to survive
Naive B cell
recirculates through secondary lymphoid tissues until it recognizes antigen
Anergic B cell
enters lymphoid tissue but excluded from follicles so they die
B cell activation/differentiation is triggered by
binding of mature B cell surface Ig to antigen from pathogen
B cell activation/differentiation leads to
B cell proliferation
B cell differentiation
SHM, isotype switching
Mature B cells encountering antigen form
germinal centers
Germinal centers
Affinity maturation
Memory B cells
Affinity maturation
only SHM and isotype switched B cells are selected for high affinity surface Ig and complete differentiation into plasma cells
make high affinity Abs
Memory B cells
Quiescent, permanent, high affinity and isotype switched Abs as immune response
Easily stimulated
B cell tumors arise from
a single transformed cell
Multiple myeloma
In bone marrow
Mutated Ig V gene
