generation of diverse and clonally expressed B-cell receptors in the bone marrow
alteration, elimination, or inactivation of B-cell receptors that bind to components of the human body
promotion of a fraction of immature B cells to become mature B cells in the secondary lymphoid tissues
Searching for infection
recirculation of mature B cells between lymph, blood, and secondary lymphoid tissues
Activation and clonal expansion of B cells by pathogen-derived antigens in secondary lymphoid tissues
Differentiation to antibody-secreting plasma cells and memory B cells in secondary lymphoid tissue
Primary Lymphoid tissue
Secondary lymphoid tissue
lymph nodes, spleen, peyer's patches
Path of B cells in lymph
start in bone marrow and travel to secondary lymph (lymph nodes, spleen, peyer's patches)
What cell markers does a HSC have?
What is the first stage of a legit b cell?
Pro- B cell
Early pro B cell
heavy chain rearrangement starts
Late pro B cell
heavy chain rearrangment continues
Large pre B cell
heavy chain is made
Small pre b cell
light chain rearrangement starts
Imature B cell
IgM on the surface
help the B cells differentiated by maintaing contact via adhesion molecules. They produce growth factors such as SCF which interacts with Kit receptor on B cells and IL-7 which helps development of the B cells
Pro- B cell rearrangement
has two chances to make a productive gene or apoptosis occurs
Surrogate light chain
fake light chain that acts as a place holder for the heavy chain during the Pre B cell stage
sLC and heavy chain. low amounts on the cell surface. binding a ligand means survival
assembly of pre-bcr signals the cell to stop rearrangement of the other heavy chain gene
Light chain rearrangment
only one recombination event requires, but several attempts happen to make a correct gene
late pro b cell stage- functional pre- BCR
small pre B cell - functional BCR
What is rearrangment dependent on?
Ig loci is...
x-linked disease blocking b cell developent at the pre-b cell stage so there is no circulating antibodies
signals b cell development
What causes cancer
high activity of recombination and mutations leads to an increase chance of mistakes
different chromosomes fuse together
B- 1 cells
atypical subset of b cells that are made early in embryonic development. CD5 cell surface protein is a marker. antibodies are not diverse and tend to bind to many antigens
B-1 cells in adult
persist in the lymphoid tissue and can self renew
Goal of selection
eliminate potentially self reactive B cells
How is selection done?
b cells that bind to self antigen in the bone marrow and periphery will die or become in active.
What happens when a b cell is self reactive?
it is retained in the bone marrow and can change its BCR
What leaves the bone marrow?
immature B cell that is expressing IgM and IgD
self reactive b cells reduce IgM and expression of rag proteins. Light chain is rearranged to make a new BCR
What are the two outcomes of receptor editing?
new BCR is not self reactive and will develop further; new BCR is self reactive and will continue rearranging until it runs out of attempts
self reactive b cells eventually die and are cleaned up by macrophages
What happens when an immature B cell binds to monovalent or soluble self antigens?
it becomes anergic and enters the periphery to die
How do B cells enter the lymph node
a homing mechanism using HEV; naive b cells bind to chemokines secreted by stomal cells.
Where do B cells congrigate when they enter the lymph node
Follicular dendritic cells (FDC
secrete cytokines that stimulate survival and differentiation
differentiation signal; transforms immature B cells that enter follicle (d + m+++) to become mature b cells (d+++ m+)
What happends to b cells that are anergic?
they are stuck in the t cell area
why is there a competition to enter the primary follicle?
entry will increase life time of cell- majority dont enter
What happens if antigen binding occurs?
b cells recognizing are detained in the t cell area; cd4 t cells will help activate the b cells to plasma cells
very specialized; protein synthesis and secretion is highly developed and they lose MHC II and BCR expression
activated b cells
formed by primary focus and migrates to primary follicle and then eventually becomes a secondary follicle
Germinal center b cells
differentiate and reside in the medullary cords, spleen, and bone marrow
B cell cancer type
is associates with the b cell stage of the tumor
Acute lypboblastic leukemia
tumor of the lymphoid protenitor located in bone and blood marrow; Ig V gene is unmutated
tumor of mature memory b cell which is in the periphery and has mutated Ig v genes, and intraclonal variability
tumor of plasma cell located in the bone marrow with mutated, no ig v genes, no variability within clone