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The B cell antigen receptor (BCR) is found to be non-randomly organized at nano-scale distances on the B cell surface. Studying the organization and relocalization of the BCR is thus likely to provide new clues to understand the activation of the BCR. Indeed, with the in situ Fab proximity ligation assay (Fab-PLA), we now obtain proofs for the dissociation activation of BCRs and start to gain insight into how the relocalization of B cell surface signaling molecules could activate the cells. This chapter describes our methods to study the nano-scale organization of B cell surface receptors and co-receptors with Fab-PLA.