**3. Development and differentiation of B cells as PC precursors**

B cells and PCs as their terminally differentiated stage play an essential role in humoral immune response. The antigen-dependent phase of B cell differentiation has been extensively studied for many years. Mature naive B cell (CD19+ CD38+/-CD20+ CD27- IgM+ IgD+ ) pass from the circulation into lymph nodes. Recognition of antigen presented on a follicular dendritic cell together with a costimulatory signal from a specific T lymphocyte causes B cell activation [15,16]. The activated B cell either migrates to extrafolicullar areas where it differentiates into a short term plasma cell or moves into a lymphoid follicle to establish a germinal centre (GC) [17,18]. Massive proliferation of B cell, somatic hypermutation of variable region of Ig chains, isotype switch and subsequent affinity maturation occur in GC [19,20,18,16]. The aim of these processes is to generate B cells able to bind the appropriate antigen with a high affinity. Part of these cells then differentiate into plasmablasts (CD19+ CD38++CD20- CD138- CD27+ ) migrating into the bone marrow where they mature into long-lived PCs (CD38+ CD138+ ) producing highaffinity antibodies. The second group differentiate into long-lived memory B cells (CD19+ CD38+/-CD20+ CD27+ IgM-/+IgD-/+) [21-23]. Besides these GC derived memory B cells also exist memory B cells lacking their typical marker CD27 (CD19+ CD38+/-CD20+ CD27- IgM+/-IgD- ) [24], which likely arise independently from the germinal center reaction [25].

Different maturation stages of B cells give a rise to a variety of B cell lymphoproliferations including post-germinal centre (post-GC) neoplasms [26-28]. Knowledge of B and PC pheno‐ type is thus important for determination of PCD diagnosis and its discrimination from other haematological malignancies (Fig 1).

**Figure 1. Coexistence of B-CLL and MM.** Clone of B-CLL is represented by CD19+CD38- CD138- B cells (turquoise dots) with cytoplasmic κ expression; clone of myeloma cells (red dots) are typical CD38+CD138+CD56+ PCs with cytoplasmic λ expression.
