| A | B |
|---|
| -provide specialized microenvironments for B cells at various stages of maturation. -they make specific contacts with the developing B cells through the interaction of adhesion molecules and their ligands -they produce growth factors that act on the attached B cells | stromal cells |
| 1:3 chance of maintaining correct reading frame. Every b cell has two copies of the immunoglobulin heavy chain locus, which means they have a chance of making a productive rearrangement on one chromosome if the other chromosome makes a nonproductive rearrangement. if the b cell has two nonproductive rearrangements then the cell dies in bone marrow | pro b cell rearrangement of heavy chain locus is an inefficient process |
| -monitors the quality of immunoglobulin heavy chain: 1. if the μ chain assembles a functional ___ it sends a signal through Igβ to shut down gene rearrangement at the immunogobulin heavy chain locus and drive the pro-B cell into proliferation 2.if the μ chain assembles poorly with the surrogate light chain and fails to make a functional ___, the cell is not given the signal to survive and dies by apoptosis | pre-B-cell receptors |
| -pre B cell receptor prevents a B cell from making more than one functional μ chain via __ -a cell expresses only one of its 2 copies of a gene -gives rise to B-cells having antigen receptors of a single specificity | allelic exclusion |
| pro-B cell where rearrangment of the first immunoglobulin locus succeeds 1.signals RAG gene transcription to stop 2. signals for rag proteins to be degraded 3.reorganizes chromatin to resist gene rearrangement | 3 effects in pre-b-cell to lead to allelic exclusion |
| the organization of the light chain loci allows initial nonproductive rearrangements at one locus to be followed by further rearrangements of the same locus that can lead to to the production of a functional light chain | Rearrangement of the light chain loci by pre-B cells is relatively efficient |
| -occurs at the late pro B cell stage with the formation, or not, of a functional pre-B cell receptor -selection for the capacity of cells to make μ chains that assemble a functional pre B cell receptor -test for functional heavy chain | B-cell development first checkpoint |
| -at the stage of the small pre-B-cell after productive and nonproductive genes have been made for the light chain. -must have the capacity to make light chains that will bind to the existing μ chain and assemble a functional B-cell receptor -test for a functional light chain | B-cell development second checkpoint |
| -the resulting population of mature B cells that do not respond to self-antigen | self-tolerent |
| -the B cell receptors of immature B-cells are wired to generate ___ when they bind to antigen -these signals cause either apoptosis or inactivation of the cell -prevents maturation of self reactive B cells | negative intracellular signals |
| -modifies the antigen receptors of autoreactive immature B-cells -light chain gene rearrangement for immunoglobulin that is not specific for self-antigen -editing continues until new non-self reactive rearrangement is made or no more rearrangement are possible and the cell dies | receptor editing |
| -self reactive B cells that react to monovalent self antigen -become inactivated and unresponsive to their specific antigen -state of development arrest in called ___ | anergy |
| IgM is prevented from assembling a functional B-cell receptor and is largely retained within the cell IgD can not activate the B cell on binding to antigen what happens to IgM and IgD in anergic cells | what happens to IgM and IgD in anergic cells |
| yes but they have a short life span 1-5 days | can an anergic cell enter the peripheral circulation |
| they interact with proteins on follicular dendritic cells that signal their final maturation | HEV=high endothelial venule PF= primary follicle FDC= follicular dendritic cells How do immature B-cells achieve final maturation? |
| they continue recirculating in the blood but soon die | what happens to immature B cells that fail to enter the primary follicle? |
| high IgM low IgD | levels of surface IgM and IgD in immature B cells |
| high IgD low IgM | levels of surface IgM and IgD in mature B cells |
| at the border between a lymphoid follicle and the T-cell area | where is the B cell activated by the T-cell to proliferate? |
| either medullary cord or bone marrow | Where do B cells from the germinal center migrate to complete their maturation into plasma cells? |
| memory B cells | B cells that leave the germinal center can also become? -establishes antigen specificites of proven usefulness permanently in the B cell repetiore |
| developmental and differentiation states | the different B-cell tumors reflect the diversity of ___ and ___ states in the normal b cell population |
| 1.migrate to the same sites in the lymphoid tissues 2.similar cell surface glycoproteins | tumor B cells and B cells similarites |
| A.stem cell B.Early pro-B cell C.Late pro B cell D.Large pre-B cell E.Small pr-B cell F.Immature B cell G.Mature B cell | B-cell development |
| IL-7 cytokine | -secreted by stromal cells and promotes growth and proliferation on late pro-B cells and pre-B cells |
| Stem cell to Immature B cell development | What process of B cell development happens in the bone marrow? |
| Immature B cell to Mature B cell to Plasma cell or Memory cell | What process of B cell development happens in the periphery? |
| kappa | What comes first kappa/lambda chain? |
| FLT3 | Signaling in stem cell protein |
| Kit, IL-7 receptor, CD25 | growth factor receptors in b cell development |
| RAG 1 and 2 | Kit, IL-7 receptor, CD25 |
| TdT | N-nucleotide addition proteins |
| λ5 and VpreB | surrogate light chain components |
| Igα and Igβ, Btk, CD19, CD45R | Signal transduction proteins |
| CD43, CD24, BP-1 | differentiation markers |
| E2A, EBF, Pax-5 | transcription factors |
| receptor editing- binding to self antigen in bone marrow cause B cell to rearrange light chain loci to make new receptor with non-self specificity | How do you eliminate self reactive clones? |
| 1. receptor editing 2. become anergic 3. apoptosis | How do you make B cells tolerant? |
| What markers are useful to identify B-cell tumors? | What markers are useful to identify B-cell tumors? |
