B cell development and differentiation occurs in multiple phases. The initial, antigen-independent phase generates mature, immunocompetent B cells that can bind to a unique antigen. This stage of development occurs in the bone marrow and involves progenitor B cell proliferation and V-(D)-J gene rearrangement, which produces clonally-unique, immunoglobulin variable regions that specifically bind antigen. B cells complete further, antigen-independent maturation into immunocompetent naïve mature follicular B cells in the bone marrow and spleen. The antigen-dependent phase of B cell development occurs following B cell activation by antigen binding and co-stimulation. These signals promote B cell differentiation into either memory B cells or terminal, antibody-secreting plasma cells. The antigen-dependent phase of B cell development involves activated B cell proliferation, antibody affinity maturation, and antibody class switching, all of which occurs in the germinal centers of secondary lymphoid tissues. Multiple cell surface-associated proteins and transcription factors are required for each stage of B cell development and differentiation.