Abstract
Expression of the membrane-bound form of the immunoglobulin (Ig) as part of the antigen receptor is indispensable for both the development and the effector function of B cells. Among five known isotypes, IgM and IgD are the common B cell antigen receptors (BCRs) that are co-expressed in naïve B cells. Despite having identical antigen specificity and being associated with the same signaling heterodimer Igα/Igβ (CD79a/CD79b), IgM and IgD-BCR isotypes functionally differ from each other in the manner of antigen binding, the formation of isolated nanoclusters and in their interaction with co-receptors such as CD19 and CXCR4 on the plasma membrane. With recent developments in experimental techniques, it is now possible to investigate the nanoscale organization of the BCR and better understand early events of BCR engagement. Interestingly, the cytoskeleton network beneath the membrane controls the BCR isotype-specific organization and its interaction with co-receptors. BCR triggering results in reorganization of the cytoskeleton network, which is further modulated by isotype-specific signals from co-receptors. For instance, IgD-BCR is closely associated with CXCR4 on mature B cells and this close proximity allows CXCR4 to employ the BCR machinery as signaling hub. In this review, we discuss the functional specificity and nanocluster assembly of BCR isotypes and the consequences of cross-talk between CXCR4 and IgD-BCR. Furthermore, given the role of BCR and CXCR4 signaling in the development and survival of leukemic B cells, we discuss the consequences of the cross-talk between CXCR4 and the BCR for controlling the growth of transformed B cells.
Highlights
B-lymphocytes (B cells) are central to the mammalian humoral immune response, as they produce and secrete immunoglobulins (Igs), known as antibodies that contribute to neutralization, fixation, and clearance of pathogens
We explain how nanocluster assembly of different B cell antigen receptors (BCRs) isotypes on mature B cells supports their functional differences. In light of this isotype-specific segregation, we address the interaction between BCR isotypes and co-receptors as well as the consequences of these processes in B cell activation and B cell-related diseases
These alterations in IgM and IgD-BCR expression in the mature B cell compartments point to a potential difference in the strength of signals generated through these two BCR isotypes
Summary
B-lymphocytes (B cells) are central to the mammalian humoral immune response, as they produce and secrete immunoglobulins (Igs), known as antibodies that contribute to neutralization, fixation, and clearance of pathogens. IgM and IgD Functional Differences the random rearrangement of the IG-gene segments in the course of early developmental stages [6,7,8] This process generates a highly diverse pool of naïve B cells carrying arrays of specificities, which could theoretically distinguish >1014 different nonself molecular monograms or antigens [9, 10]. IgA-BCR is relatively common in human but rare in mouse, while IgE-BCR is completely underrepresented in both species [26,27,28] This might indicate that BCR isotypes possess different affinity for distinct antigens, that they own different signaling capacities or that they are specialized for specific antigen forms [4, 20, 22, 23].
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