New pGen-SHM Plot Visualizes Humoral Immune Recovery After Stem Cell Transplantation
Researchers at Kobe University Hospital have developed a new analysis method called the pGen-SHM plot to track humoral immune recovery after allogeneic hematopoietic stem cell transplantation. Published online in Blood Immunology & Cellular Therapy on August 3, 2026, the technique combines B-cell receptor generation probability with somatic hypermutation rates to visualize immune maturation in two dimensions.
- The pGen-SHM plot integrates generation probability and somatic hypermutation rates to assess B-cell repertoire maturation after transplantation.
- Cord blood transplant recipients showed a two-year shift toward healthy adult repertoire patterns, while bone marrow transplant recipients displayed two distinct early populations.
- Conventional diversity indices previously failed to show clear temporal relationships with immune reconstitution, a limitation this two-dimensional mapping addresses.
Tracking Immune Reconstitution Challenges After Allogeneic Transplantation
Monitoring humoral immune recovery is essential for guiding infection prevention and revaccination strategies. However, conventional assessments rely primarily on immune-cell counts or immunoglobulin G levels, which fail to reveal whether a broad population of B cells capable of responding to pathogens has developed and matured. To address this diagnostic gap, Associate Professor Yohei Funakoshi, Associate Professor Kimikazu Yakushijin, and Professor Hironobu Minami of the Division of Medical Oncology/Hematology at Kobe University Hospital, alongside Associate Professor Goh Ohji of the Division of Infectious Disease Therapeutics and Takaji Matsutani of Anymics Inc., investigated the utility of complete B-cell receptor repertoires.
pGen-SHM Plot Maps B-Cell Receptor Sequences
To overcome the limitations of single-measure diversity indices and complementary determining region 3 length calculations, the research team developed the pGen-SHM plot. The method maps individual B-cell receptor sequences across two specific axes. First, it calculates pGen, estimating the probability that a specific receptor amino acid sequence would arise through this recombination process. Second, it measures the somatic hypermutation rate, reflecting antigen-driven maturation. Using kernel density estimation, the plot visualizes the repertoire distribution via color intensity. Immature repertoires characteristically cluster in high-pGen, low-SHM zones, while mature repertoires shift toward lower pGen and higher SHM values.
Cord Blood and Bone Marrow Repertoire Maturation Patterns
The research team longitudinally evaluated peripheral-blood B-cell receptor repertoires from six patients who underwent cord blood transplantation through 21 samples collected between 67 and 662 days post-transplant, alongside six patients who underwent bone marrow transplantation through 14 samples collected between 67 and 628 days post-transplant. In cord blood transplant recipients, high-pGen and low-SHM sequence proportions exhibited a strong inverse correlation with time elapsed since the procedure. Over approximately two years, their distribution converged toward ranges observed in healthy adults. Conversely, bone marrow transplant recipients exhibited two distinct cellular populations within the first 180 days. Samples collected on days 67, 130, and 149 displayed a low-pGen, high-SHM population alongside a high-pGen, low-SHM population. Further analysis linked the former to mature B cells in the graft, and the latter to maturing B cells newly generated from hematopoietic stem cells.
While the pGen-SHM plot successfully visualizes continuous maturation and coexisting populations that evade detection by conventional metrics, the research team intends to validate the method further. If validated, the approach may extend beyond transplantation to monitor humoral responses in vaccination, infectious diseases, cancer immunity, and autoimmune disorders.
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