Plasma cells producing a truncated γHC are highly sensitive to bortezomib. (A) Absolute number of spleen plasma cells in nontreated and bortezomib-treated mice. Each dot represents a mouse and numbers indicate the overall means of fold decrease in each strain (n = 8-17 mice). (B) Fold decrease of spleen plasma cells on 48 hours of bortezomib treatment. Each dot represents the fold decrease of plasma cell number (CD138⁺/B220^low cells) in an independent experiment with ≥2 treated and 2 nontreated mice. Means ± SEM are shown (n = 4-6 independent experiments; **P < .01; ***P < .001). (C) Quantitative transcriptional analysis of ER stress markers in (left) 4-day LPS-stimulated B cells and (right) sorted CD138⁺ spleen plasma cells from DH (white bars), WT (light gray bars), and DH-CH1⁻ (dark gray bars) mice. Results are means ± SEM of 3 independent experiments with (B) 2 mice of each strain and (C) 2 experiments of sorted plasma cells. ns, not significant; *P < .05; **P < .01; ***P < .001). (D) Gel electrophoresis of reverse transcriptase-polymerase chain reaction detecting full-length unspliced (u) and spliced (s) forms of Xbp1 in 4-day (upper) LPS-stimulated B cells and (lower) sorted CD138⁺ spleen plasma cells from WT, DH, or DH-CH1⁻ mice. Numbers indicate the ratios of Xbp1s/Xbp1u. (Lower right) An example of quantification of band intensities is shown. The upper unspecific band was excluded from the calculation. Glyceraldehyde-3-phosphate dehydrogenase was used as a loading control. L, 100-bp ladder.