B lymphocytes are a critical part of the adaptive immune response elicited by the immune system to fight various pathogens. The main effector function of the B lymphocytes is the ability to secrete antibodies, whether nonclass-switched immunoglobulin M (IgM) or class-switched immunoglobulin isotypes. To understand the function of B cells in vivo, mice are subjected to bone marrow depletion (using radiation or chemical radiation) before being adoptively transferred with donor bone marrow. Alternatively, B cells can be isolated from spleens and adoptively transferred to B-cell-deficient recipient mice to demonstrate function. In this chapter, we will outline the protocol used to isolate and transfer B cells to B-cell-deficient (μMT−/−) mice in vivo to study their functions.