B-cell Maturation Flashcards
What are the stages of B cell development in the bone marrow?
- Progenitor B cell (Pro-B cell)
- Pre-B cell
- Immature B-cell
How are the Pro-B cells further subcategorized?
- Pre-pro B
- Early pro B
- Late pro B
What is the immunophenotype of Pro-B cells?
- CD34+
- CD43 +
- CD117 +
- CD45+
- CD79a+
- CD10+
- TdT+
Note: CD19 expression is gained by the early Pro-B cells
How are the Pre-B cells further subcategorized?
- Large pre-B
- Small pre-B
What occurs in the transition from Pro-B cells to Pre-B cells?
- VDJ rearrangement of the heavy chain locus
- therefore, the Pre- B cell has cytoplasmic u heavy chains
What occurs in the transition from Pre-B cells to Immature B cells?
- Pre-B cells rearrange their immunoglobulin light chains (VJ segments)
- therefore, Immature B cells have surface IgM+
What happens to the immature B cells?
- they enter the circulation and become mature, naive B cells with surface expression of IgM and IgD
- T1 immature B cells
- T2 immature B cells
What is the immunophenotype of the immature B cells?
- CD19+
- CD43 -
- CD79a+
- CD25 -
- CD117 -
- CD34+
- IgM+
What is characteristic of the T1 immature B cells in the bone marrow?
- located in the bone marrow
- short half life
- IgM ++, IgD-, CD21-, CD23 -
What is characteristic of the T2 immature B cells ?
- they leave the bone marrow and enter the spleen follicles and acquire IgD, CD21, and CD23
- they are able to circulate and become mature, naive B cells
- once they mature they express: CD22, CD24, and CD40
In the spleen, the B cells can be subdivided into Follicular B cells and Marginal zone B cells. What are their immunophenotypes?
- Follicular: CD19+, IgM dim+, IgD bright+, CD21 moderate, CD23+
- Marginal: CD19+, IgM bright+, IgD dim+, CD21 bright, CD23-
When do the expression of Pax5 and CD79a occur in B cells?
- at the time of heavy chain gene rearrangement
- transition from Pro-B cell to Pre-B cell
When does the expression of CD20 occur in B cells?
- at the time of light chain gene rearrangement/ immunoglobulin formation
- in immature B cells
What is the phenotype of Naive B cells (mature)?
- CD19+
- CD20+
- CD5+
- sIgM+
- CD34 -
- TdT -
What markers do early hematogones express?
(+)
- CD19, TdT, CD34, HLA-DR
- bright CD10 and CD38
What markers are altered as the hematogones transition to intermediate hematogones?
- gradual loss of CD34 and CD10
- still maintain CD38
When does down-regulation of CD38 occur in hematogones?
- down-regulation of CD38 occurs in late hematogones and mature B cells
Note: CD38 is picked up again in germinal centers
What is the pattern of expression of HLA-DR in intermediate hematogones?
- HLA-DR becomes brighter
When does the loss of HLA-DR occur?
- marks the transition from late hematogones to mature B cell
In terms of hematogones, when does CD20 get acquired?
- starts to be acquired in the intermediate stage with bright expression in the late hematogones and then mature B cells.
Is there surface light chain expression in B-ALL?
- should be absent in majority of cases
What is the pattern of expression of CD9?
- positive heterogeneous expression in hematogones
- usually a positive tight cluster in B lymphoblasts
What can be the pattern of CD20 expression in B-ALL?
- CD20 can be heterogeneously expressed in B-ALL
Are myeloid markers ever present in B-ALL?
- yes, but not lineage defining (MPO), or would have to consider an MPAL
- markers for CD13, CD33 and CD117 can be seen in rare cases
