This study looks at what happens after cladribine, which is more of less the same as happens with alemtuzumab and HSCT but perhaps with different kinetics. when you deplete a B cell with anti-CD20 depleter, alemtuzumab and cladribine the circulating naive and memory cells disappear and the memory cells stay disappeared and the naive B cells get replaced by new immature and also naive B cells, so the variation of the remaining repopulation B cells expands….when you deplete T cells with alemtuzumab, HSCT and here cladribine the naive and Memory T cells get hit but the remaining mory T cells expand by a process calle homeostatic proliferation so a restricted T cell repertoire should emerge…In this study with cladridine you can read what they found and yep it is just as should be predicted. The memory B cell repertoire drops saying that some memory B cells disappear.
In the paper they suggest that “our data 12 months after completion of 2 cladribine cycles now indicate numerously reconstituting naive-like B cells in relapsing patients, which could suggest an association between a high potential for B-cell reconstitution /−differentiation and recurring disease activity.” This one view the other view would be not recurring disease but the potential to give vaccine responses
EM, Lünemann JD, Wiendl H, Klotz L, Schwab N. Confined B-Cell Reconstruction and High T-Cell Clonality Define Clinical Response to Cladribine Treatment. Ann Neurol. 2026 Jan 23. doi: 10.1002/ana.78165.
Cladribine tablets are approved for relapsing multiple sclerosis, mediating their clinical effect by moderately depleting lymphocytes. In a prospective, monocentric study including 22 patients completing 2 annual cycles of cladribine, B- and T-cell receptor repertoires and relapse activity were assessed at baseline and after 24 months. T-cell clonality increased, driven by loss of low-frequency, naive clonotypes, and re-expansion of dominant CD8 memory clonotypes, particularly in clinically stable patients. In contrast, B-cell receptor richness increased because of reconstruction by transitional and naive B cells with higher clonotype numbers observed in relapsing patients. Therefore, competing immune reconstitution following cladribine therapy could result in differential clinical responses. ANN NEUROL 2026.
Source: multiple-sclerosis-research.org