the development of b lymphocytes

phase 1 - repertoire assembly

generation of diverse and clonally expressed b-cell receptors in the bone marrow

phase 2 - negative selection

alteration, elimination, or inactivating of self-reactive b cell receptors that bind self-antigens (human cells)

75% immature b cell respond to self antigen

• retained in bone marrow

phase 3 - positive selection

a fraction of immature b cells go to secondary lymphoid tissue through the blood to mature

phase 4 - searching for infection

recirculation of mature b cells between lymph, blood, and secondary lymphoid tissues

phase 5 - finding infection

activation and clonal expansion of b cells by pathogen-derived antigens in secondary lymphoid tissues

phase 6 - attack infection

differentiate into plasma cells and memory b cells in secondary lymphoid tissue

from hemopoietic stem cell → pro b cell

1. hemopoietic stem cell (CD34)

2. common lymphoid progenitor (CD34 + CD10)

3. b cell precursor (CD34 + CD10 + CD127)

4. pro b cell (CD34 + CD10 + CD127 + CD19)

earliest identifiable cell of the b cell lineage

pro b cell

1st stage of b cell development

lymphoid progenitor cell has VLA-4 which binds to VCAM-1 on bone marrow stromal cell. there is also other cell-adhesion molecules (CAMs)

2nd stage of b cell development

early pro b cell will have KIT which binds to SCF on the bone marrow stromal cell. allows b cell to proliferate

3rd stage of b cell development

late pro b-cell: IL-7 will be released from stromal cell. allows b cell to proliferate and grow

4th stage b cell development

pre b cell: there will be surface expression of b cell receptor. the small pre b cell becomes mature

how is the pre b cell receptor diff from the mature one

it has surrogate light chain instead of regular one. surrogate made of VpreB and delta 5. usually the receptor inside the cell in a membrane-enclosed vesicle

what are the 2 checkpoints that determine fate of igm b cell while they develop in bone marrow

1. after heavy chain gene rearrangement, which promotes diversity in pro b cell population, the functional mu chain will be able to bind to surrogate light chain. if not able to, apoptosis

2. after light chain gene rearrangement, which promotes diversity in pro b cell population, the functional light chain will be able to bind to mu chain and form receptor. if not able to, apoptosis

stem cell → mature b cell

1. stem cell

2. early pro b cell

3. late pro b cell

4. large pre b cell - heavy chain rearrangement, has surrogate light chain

5. small pre b cell - light chain rearrangement

6. immature b cell - igm (first class of antibody produce) can travel from bone marrow

7. immature b cell (Mu high, delta low) - enter primary lymphoid follicle and mature, igm and igd, both have same binding site

8. mature naive b cell - (Mu low, delta high) enter circulation and bind to specific antigen

if the immature b cell is self-reactive in the bone marrow what happens

• light chain gene rearrangements to delete the gene causing the self-reactive chain and possibly creating one that is not self-reactive

• if light chain rearrangements don’t work, apoptosis 

• if binds to monovalent self antigen (antigen w/ 1 binding site) it will be in an anergic state, no rearrangements no immediate apoptosis, but unresponsive to self-antigen until a couple days later it dies

are kappa or delta light genes done first for mu heavy chain

kappa

how does immature b cell turn into mature

1. stromal cells will release chemokines CCL21 to attract immature b cell from blood vessel to HEV

2. CCL21 and CCL19 attract b cell into lymph node in t cell area

3. CXCL13 released by dendritic cells attracts b cell into primary follicle (b cell area)

4. immature b cell interacts with cell-surface components of dendritic cell to mature 

5. if mature b cell does not find antigen in primary follicle, it leaves through efferent lymphatic vessel and recirculates through blood, lymph node, and secondary lymphoid tissue. if immature cell does not enter follicle, it also enters circulation but dies

mature b cell → memory cell

1. mature (Mu low, delta high) - enter circulation and binds to antigen specifically

2. antigen-activated b lymphoblast - triggers alternative splicing to create plasma cells

3. antibody-secreting plasma cells - fight current infection

4. memory cell - prepares for future infection

Light chains contain V and J segments, whereas heavy chains contain V, D, and J segments.

true