B-cell differentiation. The first step of B-cell engagement is characterized by an IGHDH-JH rearrangement, followed by a VH-DH-JH fusion. If “productive” (or successful), these IGH rearrangements are followed by recombinations of the IGLκ, and/or IGLλ genes. These DNA rearrangements take place within the bone marrow and are totally antigen independent. The B cells then migrate to the secondary lymphoid organs where, within the germinal centers, they terminate their differentiation through the SMH and CSR processes. This differentiation step is antigen dependent, in cooperation with dendritic and T cells. The oncogenetic event is supposed to take place after this long differentiation process, before the migration of the plasma cell to bone marrow.