Figure 2.

CD21^lo B cell responsiveness is dependent on how antigen is presented. CD21^lo B cells expressing CD11c, T-bet (TBX21), and FCRL5 also express increased levels of inhibitory receptors, such as FcγRIIB. In the context of B cell receptor (BCR) ligation, FcγRIIB reduces the engagement of CD19 with the BCR, thus preventing down stream signaling, leading to hyporesponsiveness. In contrast, CD21^lo B cells binding to membrane arrayed antigens establish an immunological synaps that excludes FcγRIIB. This allows CD19 to engage the BCR and promote downstream signaling, leading to transcription of IRF4 that in turn can drive differentiation to antibody secreting cells. The membrane-arrayed antigens also lead to improved antigen-uptake and could potentially enhance the B cell antigen-presenting cell functions.