Makkar Himani, Remick Sophie, Roy Sukanya, Zangle Thomas A, Roy Koushik
Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT 84112.
Department of Chemical Engineering, University of Utah, Salt Lake City, UT 84112.
bioRxiv. 2025 May 25:2025.05.20.655194. doi: 10.1101/2025.05.20.655194.
Marginal zone (MZ) B cells are considered to be innate-like immune cells, and follicular (FO) B cells are considered to be adaptive immune B cells. Yet, the proliferative response of MZ and FO B cells to different innate stimuli remains unclear. Here, we investigated cell growth, division, and death to determine the collective proliferative response of MZ and FO B cells in response to innate stimuli, LPS and CpG. We show that the growth rate of FO B cells is higher than that of MZ B cells in response to CpG, though MZ B cells acquire a higher mass at division, whereas both the growth rate and mass at division for MZ and FO B cells remain similar in response to LPS stimulation. We show that MZ B cells divide faster and induce a higher cRel expression in response to both CpG and LPS stimulation than FO B cells. A higher proportion of MZ B cells enter first division in response to LPS stimulation, not in response to CpG stimulation, than FO B cells. Interestingly, CpG stimulation, not LPS stimulation, leads to higher cell death in MZ B cells than FO B cells. In response to LPS stimulation, MZ B cells show a higher cell number at early time and a reduced/similar cell number at late time, whereas in response to CpG stimulation, MZ B cells show a lower cell number at both early and late time. Our study suggests that LPS and CpG stimulation impact cell growth, division, and death differently, which in turn regulate different proliferative responses of MZ and FO B cells. Thus, our study offers a new perspective that different innate stimuli regulate different features of proliferative responses.
边缘区（MZ）B细胞被认为是固有样免疫细胞，而滤泡（FO）B细胞被认为是适应性免疫B细胞。然而，MZ和FO B细胞对不同固有刺激的增殖反应仍不清楚。在此，我们研究了细胞生长、分裂和死亡情况，以确定MZ和FO B细胞对固有刺激脂多糖（LPS）和CpG的集体增殖反应。我们发现，在对CpG的反应中，FO B细胞的生长速率高于MZ B细胞，尽管MZ B细胞在分裂时获得了更大的质量，而在对LPS刺激的反应中，MZ和FO B细胞的生长速率和分裂时的质量保持相似。我们表明，与FO B细胞相比，MZ B细胞在对CpG和LPS刺激的反应中分裂更快，并诱导更高的cRel表达。与FO B细胞相比，更高比例的MZ B细胞在对LPS刺激而非CpG刺激的反应中进入第一次分裂。有趣的是，与FO B细胞相比，CpG刺激而非LPS刺激导致MZ B细胞中更高的细胞死亡。在对LPS刺激的反应中，MZ B细胞在早期显示较高的细胞数量，在后期显示减少/相似的细胞数量，而在对CpG刺激的反应中，MZ B细胞在早期和后期均显示较低的细胞数量。我们的研究表明，LPS和CpG刺激对细胞生长、分裂和死亡的影响不同，进而调节MZ和FO B细胞的不同增殖反应。因此，我们的研究提供了一个新的视角，即不同的固有刺激调节增殖反应的不同特征。
