Hairy Cells As Memory B Cells

It is well established that HCs are mature clonal B cells that express a range of B-cell markers (e.g., CD19, CD20, CD22) together with surface immunoglobulin which has often undergone class-switch recombination and relatively low levels of somatic hypermutation (Table 29.1). Moreover, individual HCs can express multiple heavy chain isotypes that are generated by splicing of long RNA transcripts.1 Studies of a limited number of cases failed to show clear evidence of biased VH gene segment usage or cell selection by antigen(s).2

Table 29.1 HCs as mature B cells

• Express strong surface immunoglobulin

• All heavy-chain isotypes except IgE potentially expressed; IgG3 predominant

• Coexpression of multiple isotypes the result of RNA splicing

• Often VH mutated without further clonal evolution

• No clear biased usage of VH gene segments

• Lack naive (e.g., CD23) and germinal centre antigens (e.g., CD10, BCL-6)

• Do not express plasma-cell markers (MUM-1, CD138, BLIMP 1)

Although HCs express the plasma-cell antigen PCA1,3 and the CD85 expressed by plasma cells and other mature B cells, they have little or no propensity to differentiate into antibody-secreting cells. Recent gene expression profiling clearly places HCs, along with chronic lymphocytic leukemia (CLL) cells, at the memory stage of B-cell development.4 Reactivity with a phage-derived antibody known as phab V-3 and high levels of CD 11c expression indicate that HCs may originate from a subpopulation of normal CD11c-positive memory B cells with similar phab V-3 reactiv-ity.5 This subpopulation is VH-mutated and possesses the memory-cell marker CD27 that has also been reported to be present on HCs.4

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