CHAPTER 5.2: STAGES OF B AND T CELL DIFFERENTIATION Flashcards
Proteins that appear on cell surfaces can be used as markers to differentiate
T cells and B cells
Proteins can also be used to distinguish the developmental stages of the two types of cells according to when these proteins appear
• It acts as a reference in standardizing names of membrane proteins found on all human white blood cells
CLUSTER OF DIFFERENTIATION
• Give rise to a lymphoid myeloid progenitor
MULTIPOTENTIAL PROGENITOR STEM CELL (MMP)
LYMPHOID MYELOID PROGENITOR
• further differentiate to a (?)
common myeloid progenitor (MPP) and common lymphoid progenitor (CLP)
give rise to erythrocytes, granulocytes (eosinophil, basophil, neutrophil), monocytes and megakaryocyte (platelets)
Common Myeloid Progenitor
• give rise to T cells, B cells, Natural killer cells and dendritic cell
Common Lymphoid Progenitor
will depend on the exposure to the different cytokines
Common Lymphoid Progenitor
B Cell Differentiation
- Pro-B cell
- Pre-B cell
- Immature B cell
- Mature B cell
- Activated B cell
- Plasma Cell
T Cell Differentiation
- Double negative stage
- Double positive stage
- Mature T cell
- Antigen activation
STAGES OF B CELL DIFFERENTIATION
- PRO-B CELL
- PRE-B CELL
- IMMATURE B CELL
- PRO-B CELL
During this maturation process, the first step is the (?) (most important process in pro B cell) that code for the heavy and light chains of an antibody molecule.
rearrangement of genes
- PRO-B CELL
The end result is a (?) programmed to produce a unique antibody molecule, which consists of (?)
B lymphocyte
two identical light chains and two identical heavy chains
Does not require any antigen in order to differentiate or to mature into a next stage
Antigen Independent Phase
Several transcriptions, or growth, factors are necessary to differentiate common lymphoid precursors to produce pro-B cells
Important Growth / Transcription factors for differentiation
E2A, Early B-cell factor (EBF), Paired box protein (PAX) and Interleukin-7
Important Growth / Transcription factors for differentiation
CD19, CD45R, CD43, CD24 and c-Kit
Distinctive Markers
terminal deoxyribonucleotide transferase (TdT) -important in antibody construction
Intracellular Proteins
recombination-activating genes (RAG-1 and RAG-2) codes for antibody production
Intracellular Proteins
Note: rearrangement of (?) is the most important process in pro B cell
heavy chains
Begins at the synthesis of the heavy chain part of antibody
- PRE-B CELL
The first heavy chains synthesized are the μ chains, which belong to the class of immunoglobulins called IgM (monomer in pre-B cell but the circulating IgM is pentamer).
PRE-B CELL
• CD43, c-Kit and TdT
Markers and proteins lost during process
u chain, surrogate light chain and 2 very short polypeptide chains that are non-covalently associated with each other
Surface Receptors
Adhere to the bone marrow stromal cell and transmit signal to prevent rearrangement of any other heavy chain
Pre-B cell receptor
Stimulates burst of clonal expansion (continuous production)
Pre-B cell receptor
Note: rearrangement of (?) is the most important process in pre-B cell
light chains
IMMATURE B CELL
Distinguishing characteristic
Presence of complete IgM molecule in the cell surface
This indicates that rearrangement of the genetic sequence coding for light chains on either chromosome 2 or 22 has taken place by this time.
IMMATURE B CELL
Completion of light chain rearrangement commits a cell to produce an antibody molecule with specificity for a particular antigen or group of related antigens.
IMMATURE B CELL
acts as a receptor for a breakdown product of the complement component C3, known as C3d
This enhances the likelihood of contact between B cells and antigen, because antigen frequently becomes coated with complement fragments during the immune response
CD21
Important for interaction of B cells with T cells.
CD40 and MHC Class II molecule
2 Destinations
• Programmed cell death (apoptosis)
• The remaining 10% leave the bone marrow and seed the lymphoid organs
There is evidence that self-antigens can give a negative signal to immature B cells resulting in arrested maturation and cell death
Immature B cells that tightly bind self-antigens through cross-linking of surface IgM molecules receive a signal to halt development, and they are eliminated or inactivated
Programmed cell death (apoptosis)
90% of B cells die in this manner without leaving the bone marrow.
Programmed cell death (apoptosis)
Takes place in the spleen
MATURE B CELL
remain in the spleen in order to respond quickly to any blood-borne pathogens they may come into contact with
Marginal Zone B cell
Lymph nodes and Other Secondary Lymphoid Organs (SLO)
MATURE B CELL
MATURE B CELL Distinguishing characteristic
Presence of IgM and IgD
same specificity for a particular antigen or group of antigens
Presence of IgM and IgD
is not required for B cell function but it may prolong the lifespan of mature B cells especially in peripheral blood
IgD
Naive B cells
Antigen-dependent phase
These B cells have a half-life of more than 6 weeks
Antigen-dependent phase
Primary Follicles of Peripheral Lymphoid tissues
Antigen-dependent activation
ACTIVATED B CELL Identifying Marker
CD25
found on both activated T and B cells
acts as a receptor for interleukin-2 (IL-2)
CD25
- a growth factor produced by T cells
interleukin-2 (IL-2)
Additional receptors that appear at this time are specific for other growth factors produced by T cells.
CD25
When B cells are activated in this manner, they transform into blasts that will give rise to both plasma cells and so-called (?).
memory cells
Not normally in the blood but are located in the germinal center of the peripheral lymphoid organs (PLO)
PLASMA CELLS
Spherical or ellipsoidal (10-20 um in size)
PLASMA CELLS
PLASMA CELLS Characterized by
Abundant cytoplasmic Immunoglobulin
Nucleus: eccentric or oval (heavily clamped chromatin-stains dark)
Abundant ER and well-defined golgi zone
are nondividing, and after several days of antibody production, they die without further proliferation
Plasma cells
Capable of responding to antigens with speed and intensity
MEMORY CELLS
Has longer life span
MEMORY CELLS
Represents progeny of antigen stimulated B cells
MEMORY CELLS
Similar in appearance with unstimulated B cells
MEMORY CELLS
They remain inactivated for months or years and ready to respond to antigen
MEMORY CELLS
Found in germinal layer
MEMORY CELLS
Sixty to 80 percent of circulating lymphocytes in the peripheral blood are (?), and these become differentiated in the (?).
T cells
thymus
– site of differentiation
Thymus