B cell differentiaton

In the earliest B cell lineage, Ig genes of pro-B cells exist in a germline configuration.
Early B cell factor 1 (EBF1) is one of the key transcription factors  organize B cell lineage
development.
During the differentiation of pro-B cells into a pre-B cell, a rearrangement in the heavy chain
locus begins (occurs at both alleles of the heavy-chain locus)
Once these rearrangements are successfully completed, transcription begins produce mature
mRNA encoding the μ heavy chain  late pro-B cell becomes a pre-B cell.
During the pro-B and pre-B stages, not only is H chain and L chain Ig rearrangement occur, but
each stage is tested to make sure that it is a functional rearrangement
+ The H chain Ig gene rearrangement is tested through the production of the surrogate L chain
that interact with a complete H chain. If it can produce appropriate signal that similar to fully
functional BCR  differentiation can continue.  
Next, the pre-B cells become immature B cells.
+ L chain gene pairs with the H chain transported to the plasma membrane and interact with
many components to signal a fully formed BCR.  
+ Negative selection: the immature B cells are “tested” for auto-reactivity. If the immature B
cell interacts with self antigens  harmful to the host  cells die by apoptosis.
Then, immature B cells (BCRs express both IgM and IgG) leave the bone marrow to the
secondary lymphoid tissues (Spleen). Once entering into the lymph node, these the immature B
cells are called transitional type 1 (T1) B cells.  .
The T1 B cells are located outside of the follicle and exposed to more self cells and circulating
proteins
+ if they respond strongly  autoreactivity  cells die
+ If they survive  they can then migrate into the follicle  become T2 B cells ( responsive to
antigen) become fully mature B cells that can participate in immune responses.  
The mature B cells will circulate through all lymphoid tissues and be exposed to antigens  B
cell activation by two different pathways: T-independent B cell activation ans T-dependent B
cell activation.
+ T-independent activation: clustering of BCRs and recognition of toll-like BCRs  activate B
cell to produce plasma cells that mainly secret IgM antibodies.
+ T-dependent activation: B cells present antigen to the T cells activate the B cell  B cells
undergo somatic hypermuttion (to increase their affinity towards antigens) and class switching
 create antibody-producing plasma cell sand memory B cells
Antibody-producing plasma cell is the terminal differentiation of a B cell:
+ if located in the lymph node: short-term plasma cells (produce antibody for a limited period
of time).  
+ if migrate to the bone marrow: long-lived plasma cells (secrete antibodies for decades)
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