Purpose of review: In this review, we describe the interaction between B cells and bone during development, aging, and disease. Recent findings: There is an increased interest in identifying the mechanisms of interaction between immune cells and the skeletal system. This knowledge is critical for understanding the pathology of autoimmune diseases and developing therapeutic interventions. Humoral immunity depends on B cells and their secreted immunoglobulin (antibodies). Earlier studies described B cell influence on the skeletal system, with a major focus on the role of plasma cells and secreted antibodies. The contribution of bone marrow developing B cells to the skeletal system was still poorly studied and represents a gap in our knowledge. This is an active area of investigation in our research group. The crosstalk between B cells and bone starts as early as the commitment of hematopoietic stem cells to the B cell lineage and the differentiation of mesenchymal stem cells to osteoblast progenitors. This crosstalk is active during different developmental stages and continues throughout the life of the individual, especially since both B cells and bone cells share the same developmental niche. Summary: Bi-directional interaction of developing B cells and osteoblasts, osteoclasts, and chondroblasts ensures their normal development and functional activity. During aging, this interaction is disrupted, leading to disease progression, decreased bone mass, and osteoporosis. A better understanding of B cell-bone interactions will help identify novel immune targets that might provide therapeutic benefit for the elderly and patients.

The immune repertoire (IR) is a term that defines the combined unique genetic rearrangements of antigen receptors expressed by B and T lymphocytes. The IR determines the ability of the immune system to identify and respond to foreign antigens while preserving tolerance to host antigens. When immune tolerance is disrupted, development of autoimmune diseases can occur due to the attack of self-antigens. Recent technical advances in immune profiling allowed identification of common patterns and shared antigen-binding sequences unique to diverse array of diseases. However, there is no current literature to date evaluates IR findings in autoimmune and skin inflammatory conditions. In this review, we provide an overview of the past and current research findings of IR in various autoimmune and dermatologic conditions. Enriching our understanding of IRs in these conditions is critical for understanding the pathophysiology behind autoimmune skin disease onset and progression. Furthermore, understanding B-cell and T-cell IR will help devise therapeutic treatments in the hopes of restoring immune tolerance and preventing disease onset and progression.

Peritoneal cavity (PerC) B cells arise via a specific set of ontogenetic and antigen-driven selection pressures. A large portion of the PerC B-1 population, including B-1a and B-1b cells, is fetal-derived and thus, due to a lack of N nucleotide addition, produces an immunoglobulin repertoire that is characteristically germline-encoded. While conventional B-2 cells depend on efficient pairing of surrogate light chain (SLC) and μ Heavy Chain (HC) to pass through the preBCR checkpoint, the extent to which the passage of the B-1 population through the preBCR checkpoint affects the composition of its repertoire has remained an open question. In this work, we used mice deficient in λ5, a key component of the SLC, to test whether the absence of preBCR selection would yield natural, germline encoded, PerC B-1 CDR-H3 repertoires similar to WT. And, if not, whether a more WT-like repertoire at the protein level would be recreated by convergent cellular evolution. We found that the absence of preBCR selection led to categorical differences in DH-specific gene segment usage, RF preference, and N addition in PerC B-1a, B-1b, and B-2 CDR-H3s when compared to WT. Despite this marked divergence in nucleotide sequence, at the translated amino acid level, the B-1a CDR-H3 repertoire generated in the absence of preBCR selection exhibited partial convergence to the WT sequence, most notably with selection for tyrosine; this phenomenon was less apparent in B-1b and B-2 cells. This convergence was not evident at the nucleotide level and did not restore the underlying VDJ architecture. These results suggest that while the initial CDR-H3 repertoire is altered genetically in the absence of preBCR selection, natural self-antigen selection and self-renewal in the B-1a compartment promote the creation of a CDR-H3 repertoire that has considerable overlap in amino acid sequence with its wild-type counterpart.