CLL is characterised by the clonal expansion of CD5+CD23+ B cells which are phenotypically distinct from most normal B cell subsets. This section provides more detail as to the possible origin of CLL B cells.
Current data suggest that CLL B cells are derived from CD5+ B cells, specifically CD5+CD27- B cells with unmutated IGHVs in the case of CLL cells with unmutated IGHVs, and CD5+CD27+ B cells with mutated IGHVs in the case of CLL cells with mutated IGHVs (Zhang & Kipps, 2014).
Some healthy adults have subsets of expanded B cells (known as monoclonal B cell lymphocytosis, MBL) which have a similar surface-antigen phenotype to that of CLL cells. It is therefore thought that MBL may be a precursor of CLL. MBL is seen in approximately 13.0% of adult siblings of patients with CLL whereas it is seen in around 3.5% of adults without a family history of CLL (Zhang & Kipps, 2014). The rate of development of MBL into CLL or other lymphomas is around 1% per year indicating that additional genetic or epigenetic changes are required before becoming CLL B cells or lymphomatous cells (Zhang & Kipps, 2014).
ROR1, normally only expressed by cells during embryonic development, has been found to be expressed by CLL B cells. A subset of ROR1+ B cells expressing CD38 have high levels of the CLL markers CD5 and CD23, leading to the hypothesis that ROR1+CD38+ B cells in healthy adults may be a precursor to CLL (Zhang & Kipps, 2014).
It has been observed in xenograft transplant studies, that HSCs from CLL patients may develop into mono- or oligoclonal B cells with a CLL phenotype, but it is currently unclear as to whether these cells represent a type of stem cell for CLL (Zhang & Kipps, 2014).